Tuberculosis and liver disease

Disorders of liver function and structure in patients with tuberculosis may be a consequence of the influence of tuberculosis intoxication, hypoxemia, taking anti-tuberculosis drugs, concomitant diseases, and tuberculous lesions 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 volumetric blood flow in the organ and a slowdown in the rate of elimination of drugs. Common forms of tuberculosis can be accompanied by hepato- and splenomegaly. In general amyloidosis, developing against the background of tuberculosis, liver damage is noted in 70-85% of cases.

At the cellular level, hypoxia leads to switching the respiratory chain to a shorter and more energetically advantageous path of succinic acid oxidation, inhibition of 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 in hypoxia has been established: protein synthesis; pigment formation; prothrombin formation; carbohydrate synthesis; excretion; urea formation; fibrinogen formation; cholesterol esterification; enzymatic function. The excretory function suffers first; the absorption function is impaired only in stage III respiratory failure. There is also an inverse relationship: the addition of liver pathology to pulmonary disease aggravates the impairment of ventilation and gas exchange, which is caused by damage to cells of the reticuloendothelial and cardiovascular systems, and impaired hepatocyte function.

Combination of tuberculosis with liver damage

Liver damage is one of the main causes of drug intolerance in tuberculosis due to the leading role of this organ in the detoxification system. The incidence of toxic drug-induced hepatitis is 4-16% of complications of drug therapy, it increases with the duration of drug intake. Drug-induced hepatitis is characterized by dyspeptic, abdominal pain syndrome, hepatomegaly, sometimes icterus of the mucous membranes and sclera, skin itching; prodrome is uncommon. Inflammatory and cytolytic syndromes predominate with moderate cholestatic. Laboratory tests reveal an increase in the level of transaminases, alkaline phosphatase, cholinesterases, and less often bilirubin. When using anti-tuberculosis drugs, fulminant hepatitis may develop, the mechanism of development is immunoallergic and toxic. Developed liver dysfunctions persist for 2-4 months after the disappearance of clinical manifestations. A relationship between treatment tolerance and the patient's age has been noted. In elderly patients, it is necessary to change the treatment regimen due to side effects, and in old age - to reduce the drug doses. Data on the hepatotoxicity of anti-tuberculosis drugs are quite contradictory, since this property is associated not only with the chemical structure of the drug, but also with the features of the metabolic capabilities of the liver of each patient, the magnitude of hepatic blood flow, the level of development of portocaval anastomoses, the degree of binding of drugs to plasma proteins, etc.

The increasing incidence of combined pathology (tuberculosis and chronic non-specific lung diseases, gastrointestinal diseases, hepatobiliary system, diabetes mellitus) leads to an increasing incidence of liver damage. Over the past decades, the incidence of combined pulmonary tuberculosis and liver diseases has increased 23-fold and accounted for 16-22% of newly diagnosed tuberculosis patients and 38-42% among chronic patients. In phthisiopulmonary patients, independent liver diseases are diagnosed in 1% of cases, secondary hepatitis accounts for 10-15% of all complications of drug therapy. The structure of secondary hepatitis: 36-54% - non-specific reactive hepatitis. 16-28% - drug-induced. 3-8% - specific tuberculosis. 2% - alcoholic. The combination of pulmonary tuberculosis with liver disease of non-viral etiology proceeds unfavorably, with a tendency to progress.

With a combination of viral hepatitis B and tuberculosis, the icteric period is more severe, an increase in the size of the liver and deviations in biochemical parameters, hemogram are more often noted, there is a slowdown in the neutralization and inactivation of isonicotinic acid hydrazide (IAH), hepatotoxicity of rifampicin and pyrazinamide increases, a protracted course of hepatitis develops 3 times more often. Among patients with pulmonary tuberculosis - carriers of hepatitis B markers, hepatotoxic reactions to tuberculostatics are observed in 85% of cases, the disease is characterized by a more acute onset, a pronounced clinical picture and low treatment efficiency. The excretory function of the liver in such patients is impaired even before the start of treatment and does not normalize during anti-tuberculosis therapy. Hepatitis C damage is most typical for patients with chronic pulmonary tuberculosis. A positive reaction to antibodies to hepatitis C is considered a risk factor for the development of hepatotoxic reactions when prescribing anti-tuberculosis drugs.

People with liver cirrhosis have an increased risk of developing tuberculosis, and patients with acute tuberculosis and liver cirrhosis have a poor prognosis.

When pulmonary tuberculosis and alcoholism are combined, poor tolerance of anti-tuberculosis drugs (up to 60%) and liver damage (up to 80%) are possible. Alcohol disrupts lipid metabolism, causing fatty infiltration of the liver, reduces the intensity of metabolism of biologically active substances, inhibits protein synthesis in hepatocytes and their ability to regenerate. Direct necrobiotic effect of ethanol on the liver is possible. Such patients are characterized by toxic, toxic-allergic and not allergic reactions. With a high prevalence of toxicomania and drug addiction, one can predict an increase in the problem of hepatotoxic reactions.

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

Liver tuberculosis 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-nodular and tumor-like liver tuberculosis. The main route of liver damage is hematogenous. In miliary tuberculosis, the liver is almost always involved in acute granulomatous inflammation; liver tuberculosis requires standard systemic anti-tuberculosis therapy.

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Treatment of liver diseases in tuberculosis

Prevention of liver function damage in tuberculosis and timely correction of disorders are vitally important, since they determine the possibility of adequate chemotherapy, manipulations and operations using anesthesia.

The process of lipid peroxidation is more intense in infiltrative forms of pulmonary tuberculosis than in chronic widespread destructive ones. This dictates the inclusion of drugs with antioxidant and antihypoxic activity, protecting the liver parenchyma, in the usually used complex of therapeutic measures. They have anti-inflammatory, antifibrotic, antitoxic properties, limitation of collagen formation and activation of its resorption. Hepatoprotectors are recommended to reduce lipid peroxidation and stabilize hepatocyte membranes. Krebs cycle metabolites are used as a corrector of oxidative phosphorylation. In case of pronounced toxic reactions, cancellation of specific therapy and intravenous drip infusion of protease inhibitors are indicated. Glucocorticoids reduce the toxic effect of antibacterial drugs and, when included in complex therapy, reliably reduce the incidence of liver dysfunction. Methods of sorption detoxification and hyperbaric oxygenation have found wide application in cases of liver dysfunction.

Of great practical importance is drug-free correction of liver damage in tuberculosis. In this case, it is necessary to determine the type of acetylation - the faster its rate, the greater the damaging effect of the metabolites of the GINK. Selection of the parenteral route of administration, intermittent method of drug administration. Breaks in the administration of drugs of the GINK group for 1-2 days significantly reduce its hepatotoxicity. Dystrophic changes in the liver are observed less often if the entire daily dose of isoniazid is administered once a day, especially parenterally. The interaction of drugs can be corrected by changing the treatment regimens. When rifampicin, pyrazinamide and streptomycin are prescribed 2 times a week, the hepatotoxicity of this combination is reduced. In polychemotherapy using 4 to 7 anti-tuberculosis drugs, various regimens are acceptable, but on the condition that no more than 3-4 drugs are taken per day, and the simultaneous use of rifampicin and isoniazid, prothionamide, ethionamide, and pyrazinamide is excluded.

It should be taken into account that gastro- and hepatoprotectors themselves can affect the metabolism of drugs. In particular, allochol 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 a phthisiatrician must take into account in his work.