7.7. Tuberculosis and liver diseases


The hepatic pathological conditions at tuberculosis are grouped, as follows:

  1. Specific (tubercular) damage of liver;
  2. Damages of the hepatic cells;
  3. Reductions of functioning tissue mass.

1. Specific (tubercular) damage of liver.

The liver is commonly damaged at of miliary or disseminated tuberculosis. Less commonly, localized abscesses of the hepatic parenchyma have been noted.

Tubercular defeat of a liver at newborn.
The bacilli pass through the placenta and enter the fetal circulation. Then the bacilli penetrate through umbilical veins to the liver. Most of the infants seem well at birth but by about the third week the baby stops gaining weight and becomes jaundiced, with pale stools and dark urine. The liver and spleen are found to be enlarged. The infant has obstructive jaundice because there is a primary focus in the liver and large lymph nodes obstruct the outflow of bile at the porta hepatis. The other causes of jaundice at this period should be excluded.

Biliary tract compression (cholestasis) by tuberculous lymphadenitis of the peri-pancreatic or portal lymph nodes has been recorded. The most widely used indicator of cholestasis is content in plasma of alkaline phsphatase (AP). In cases extra-hepatic obstruction of bile passes AP contents in blood plasma are maximal. The consequences of cholestasis depend on a degree of its severity and duration. The increase of concentration in plasma of bile acids breaks resorption of fats and fat-soluble vitamins. It is possible to find out reduction of blood coagulating factors, for which synthesis fat-soluble vitamin K is necessary. This diagnostic signs could be revealed by lengthening of prothrombin time at an early stage of disease. At cholestasis accumulation of bilirubin (mainly conjugated) arises, this phenomena is usual, but not always and is accompanied by jaundice and bilirubinemia. Besides excretion of cholesterol are disturbed and its contents in blood plasma raises.

2. Damages of the hepatic cells.

2.1. HIV infection, viral hepatitis and adverse anti-tuberculosis drug reactions.
HIV infection increased Adverse Drug Reactions ( ADRs) fourfold the likelihood of perturbations of liver chemistries, viral hepatitis С infection increased the risk fivefold, and that coinfection with HIV and hepatitis С increased the risk 14-fold. Overall, however, these data observations do not change the use of standard medications including INH, the rifamycins, pyrazinamide, ethambutol, or streptomycin.

2.2. Functional damage of the liver caused by application anti-tuberculosis drugs.
The basic drugs (rifampicin and isoniazid) used for tuberculosis treatment have expressed hepatotoxic action. Many bioenergetic processes in hepatocites are broken during isoniazid biotransformation (in which microsomal enzymes of liver participate). At the same time, induced hepatopathy is caused not only its direct action on a liver, but also inclusion of the autoimmunity mechanisms. The methabolism of rifampicin occurs in liver microsomes, from which it is discharged as glycoroinids that in clinic picture can result to hyperbilirubinemia. Isoniazid and rifampicin, and also other anti-tuberculosis drugs can cause changes of hepatocytes, up to necrosis, or provoke cholestasis development. In this connection, especially dangerous is possibility of chronic liver damage development. The risk of development drug induced complications and severity of arising hepatopathy are more expressed at presence at the patients of concomitant diseases of: liver, kidneys, cardio-vascular and endocrine systems The age of the patient is essential also.

2.3. Indicators of the liver cells damage.
The liver cells damage (expressed from focus necrosis up to destruction of a significant part of the liver) causes fast discharge of intracell components into blood stream. Sensitive indicators of such damage are the concentration in plasma AST (asparate aminotransferase) and ALT (alanine aminotrasferase). The maximal levels of their concentrations in plasma are achieved at simultaneous damage of big quantity of cells.

At prediction of the liver cells damage the following two circumstances are essential:

  1. the long retain of increased, even in a small degree, trsansaminase activity in plasma specifies proceeding destruction of hepatic cells, which can result in development of chronic disease of a liver;
  2. the sudden reduction (at a previous very high level) transaminases without improvement of a clinical picture specifies destruction of significant volume of the hepatic tissue, as only alive cells can continue enzyme synthesis.

3. Reduction of the hepatic functioning tissue mass.

The functional reserves and ability to regeneration of the hepatic tissue are very big. At acute liver diseases, dominate insufficiency of excretory function and damage of the liver cells when prevailing portion of liver is damaged. Usually cell regeneration occurs quickly, before development of clinical symptoms, which indicate frustration of the liver functions. The chronic diseases of a liver can, however, result in such significant reduction of functioning tissue mass, that synthetic and metabolic functions noticeably damaged. As reserve excretory capacity is great, stayed undamaged cells can ensure excretion of prevailing bilirubin volume transported into them, due to what the jaundice is usually moderate or is absent. The revealing of the hepatic functioning tissue mass reduction among tuberculosis patients is very important, because depending on the liver condition the biotransformation of drugs can change. If the synthetic function is considerably suppressed, the albumin contents in blood plasma is lowered and prothrombin time is extended. Simultaneously the prothrombin synthesis is completely stopped even after parenteral introduction of vitamin K. When significant mass of hepatic tissue is damaged, the metabolic signs of liver insufficiency occur. It is possible to evaluate it, particular, on decrease of activity cholinesterase or pseudo-cholinesterase, which are basically synthesized in a liver and can reflect its synthetic activity.

Insufficiency of hepatocytes functions. This condition is usually accompanied by jaundice development, though in acute cases the death of the patient before occurrence of jaundice is possible. Depending on a stage of disease it is possible to find out anyone (or all) signs characteristic for hepatitis of infringement of biochemical processes.

To number of other features of this pathology concern following metabolic changes:

  1. heavy infringements of electrolytes exchange, in particular, hypopotassemia, caused by secondary hyper aldosteronism;
  2. lengthening of the prothrombin time and other infringements of blood coagulation;
  3. the reduction of urea concentration in plasma (in norm of ammonia liberated at amino acids desamidization, is used in a liver for urea synthesis).

The infringement of this process results in insufficiency urea production and subsequent amino-acidemia. In many cases kidney insufficiency develops. Despite of an oppression of urea synthesis, its contents in blood increases.

Monitoring for hepatitis.

The newly hospitalized patients go through initial examination by routine biochemical tests allowing estimating liver and kidneys conditions fora primary estimation of homeostasis and a choice of tactics of treatment. Diagnostics of the liver condition is based on definitions in the blood serum the following parameters:

  1. the contents of bilirubin – an indicator of excretory function;
  2. activity of ACT and/or ALT – an indicator of the hepatic cells damage;
  3. activity of the alkaline phosphatase – indicator of cholestasis;
  4. the albumin contents and – or definitions prothrombin time, cholinesterase activity – indicators of synthetic function (last is determined in the event that heavy hepatopathy is revealed).

In process of tuberculosis chemotherapy, the patient’s activity of tramsferases and bilirubin are repeatedly checked once in two weeks, taking into account possible influence of the drugs on the liver.

Such algorithm of the control allows:

  1. To reveal hepatic pathology during treatment before clinical signs appear, when the symptoms of the disease are not present, patient does not feel discomfort;
  2. To supervise reaction of a liver on anti-tuberculosis drugs, if any pathology took place prior to the beginning treatment.

At presence of intoxication symptoms, developing of cholestasis or toxic hepatitis at the tuberculosis patients to the above-stated analyses can be added the additional tests (definition choestasis enzymes, electrolytes, cholesterol and and/or cholinesterae), which, are necessary for correction of therapy of the basic disease with the purpose to reduce adverse drug reactions.

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