Radkov, M.

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Varna Medical University Press: Journals

DYSPROTEINAEMIA IN V I R A L H E P A T I T I S M. Radkov Key-words: dysproteinaemia — vira l hepatitis — serum immunoglobulins — diagnosis The comparison of protein metabolism data with the c l in ical course of l iver diseases enables more successfully to reveal a close relationship between the cha-racter of the changes in the course of the disease and the pathological process. Recently, the extensive analysis of the changes of the individual serum protein levels (12) becomes very important. Concerning the acute v i r a l hepatitis ( V H ) which is s t i l l a widespread infectious disease it is to be mentioned that severe alterations of l iver protein metabolism commit at the c l imax of the illness (5, 9, 10). According to Soviet authors (1) there is a decrease of total protein and albu-mins content but an increase of globulins mainly on the account of gammaglobu-l in fraction and less expressed of alpha!- and beta-globulin ones in severe V H forms. In our country some systemic investigations of protein spectrum changes were performed mostly wi th chronic hepatic diseases (2, 3, 4) . Many problems related wi th changes of the serum proteins and antibodies as indicators of the pathological process (its act ivi ty , diagnosis, differential diagnosis, and progno-sis) which are often necessary in various kinds of jaundice are not yet clarified enough if V H patients and reconvalescent persons are concerned. The practitioner is interested in the following most important and actual questions: when and in which cases V H w i l l have a protracted course, wi th exacerbations and recidives, wi th a tendency towards chronification, which are its earliest signs going before the c l in ica l symptoms or even the clinicolaboratory tests. The treatment of dys-proteinaemia in both V H and posthepatic conditions is an important stage of the complex therapy. A contemporary practitioner must be aware of these problems, solve them and make correctly his choice between immunosuppressive and immu-nostimulating drugs. The aim of the present study was to follow-up the changes of individual se-rum proteins and immunoglobulins in V H in order to get an exact notion and characteristics of the illness and to correct the present dysproteinaemia. The fol-lowing determination tasks were to be assigned: 1. Serum concentrations of pro-teins of synthesis (reflecting mainly the protein-synthetic function of the l iver) : praealbumin, albumin, transferrin, fibrinogen, fibrin-degradation derivatives D and E , serum cholinesterase, haemopexin, 2. Indexes of the acute stage of the inflammatory process: a lpha r ant i t ryps in , a l pha r ac id glycoprotein, haptoglo-b in , ceruloplasmin, (^-glycoprotein I ; p 2-glycoprotein I I (C 3 -activator). 3. Immu-noglobulin ( IgG, IgM, IgA and IgE) changes as response to antigenic irr i tat ion in V H . 4. Changes of certain proteins such as complement C , group-specific pro-tein, C 4 , C 9 , alphaj-fetoprotein, etc. \ \ \ 102 М. Radkov Material and methods The study covered 554 V H patients and 112 reconvalescent persons hospita­lized in the Cl in ic of Infectious Diseases, Higher Institute of Medicine, Varna during the period from 1970 t i l l 1980. They were divided into groups according to the following cl inical forms: a) anicteric one — 60 patients (8,88 per cent); b) slightly icteric — 205 ones (30,32 per cent); c) middle-severely icteric — 182 ones (26,92 per cent); d) severely icteric — 95 ones (14,05 per cent); e) dys­trophic — 12 ones (1,78 per cent) and f) reconvalescent — 112 ones (18,05 per cent). The following immunochemical methods based on the immunoprecipita-tion reaction were used to study serum proteins in V H : quantitative determination of serum proteins after Mancini , immunoelectrophoresis, bilateral immunodif­fusion, electrophoretical immunoprecipitation, rosette-test for Т-cell determi­nation. The data were statistically processed by using the var ia t ion and graphic analysis. Sera of 300 healthy blood donors from Varna city and the district of Varna were used as controls. Results and discussion Our investigations of the quantitative changes of indiv idual proteins and immunoglobulins in V H patients and former V H cases showed a differently expres-T a b l e 1 Comparison between the mean levels of certain individual serum proteins in VH patients positive for hepatitis В and negative for the same disease Protein Kind of hepatitis X or m x С (%) t F ( t ) Albumin hepatitis A ЗЗ27 225 290 6,76 1,730 >0,1 hepatitis В 2827 1591 289 56,34 controls 3998 181 30 4,55 Transferrin hepatitis A 271,80 211,2 21,55 79,99 0,814 >0,5 hepatitis В 194,24 92,84 16,16 47,79 controls 272,82 44,67 8,44 16,42 Fibr nogen hepatitis A 230,78 100,3 10,23 43,46 0,687 >0,5 hepatitis В 219,42 74,97 13,04 34,16 controls 393,30 27,39 9,13 6,96 <z rAnti- hepatitis A 278,26 117,3 11,76 42,05 0,170 >0,9 trypsin hepatitis В 258,10 103,9 17,08 40,25 controls 290,83 27,24 8,61 9,36 Cerulo- hepatitis A 8,49 5,84 0,54 68,88 0,115 >0,9 lasmin hepatitis В 7,37 4,58 0,79 62,17 controls 17,95 7,75 2,23 43,18 a 2-macro- hepatitis A 244,58 81,26 13,45 33,22 1,606 >0,2 globulin hepatitis В 274,55 86,75 12,87 31,45 controls 257,32 42,85 8,09 16,67 Haptoglo­ hepatitis A 164,05 115,8 12,94 70,58 2,098 <0,05 bin hepatitis В 191,81 116,2 2,86 60,58 controls 172,50 40,5 11,69 32,47 p2-glycopro - hepatitis A 11,97 2,22 0,21 18,54 0,791 >0,5/ tein I hepatitis В 12,69 5,62 0,88 44,28 / controls 7,56 1,60 0,46 21,22 C 3 -activa- hepatitis A 9,02 4,87 0,53 54,05 0,935 >tf),5 tor hepatitis В 9,97 6,38 1,18 64,00 / controls 12,19 2,34 0,67 19,21 / / Dysproteinaemia in viral hepatitis 103 )d dysproteinaemia depending on the cl inical form and the stage of the disease able 1). Mean protein levels reflecting mainly l iver capacity for protein synthe-is decreased progressively attending the hepatic damage (fig. 1). Th is was estab-ished first for prealbumin that was reduced in 93,2 per cent of the cases at the Mjf/f00ml 4000 2500 250 200 1500 C. L M H. C. L. M. H. C. L Л H. С I. M H. C. L M. H. Ppealt. Aid. Ph. Tph. Hpc. ig. 1. Changes of serum proteins reflecting predominantly protein-synthesis function of the iver in different cl inical forms of v i ra l hepatitis Mgjwomi 350 300 250 200 150 j-100 I Ш C. L M. H. ' * TP C. L. M.H. dL2M C. L. M. H. C. L M. H. cLz H5-Gp Fig . 2. Changes of serum proteins - indexes of the acute phase of the inflammatory process in different clinical forms of v i ra l hepatitis onset of the disease. Albumin was also significantly reduced. Transferrin was stat is t ical ly significantly decreased in any c l in ica l forms (p<0,01) (8). This fact is a true sign for l iver lesions in V H . Haemopexin was also significantly dimi­nished. Th i s protein is s t i l l insufficiently studied in our country. Its changes attest the disturbances of l iver protein-synthetic functions. Fibrinogen levels are so sensitive that together wi th other coagulation tests they can be used as a reliable criterion for V H prognosis. The stronger the acute massive l iver necrosis and cytolysis, the lower the fibrinogen levels. The greatest part of the individual proteins of the second group decreased, too ( i . e. alphai-antitrypsin diminished in middle-severe and severe V H forms but increased in mild cases (fig. 2). I t could be due to glycocorticosteroid suppres-104 М. Radkov sion administered to most patients because of total intoxication and hyperbili-rubinaemia. Alpha 2 -macroglobulin, one of the "heavy proteins" was reduced in any patients. The differences in single cases were insignificant. Haptoglobin de­crease could be explained wi th the diminished l iver protein synthesis in V H . MgI 100 ml 20 -16 -18 Г— 14 r C. L. M H. С L. M. H. C. L. M. H. C. L. M. H. Cp UjCGp J32GpI PiGpH(Cs) Fig . 3. Changes of serum proteins during the acute inflammatory response in different forms o f v i r a l hepatitis Mg 1100 ml C. LM. H. C. L M. H. C. L M. H. С L M H. JgS JgM JgA HE. MB. Fig . 4. Changes of serum immunoglobulins in different forms of v i ra l hepatitis Because of its short half-life its level can be used as a good indicator for l iver func­tional state concerning protein synthesis. The constant tendency towards cerulo-plasmin reduction is strongly related wi th the seriousness of the illness. Any other proteins of the glycoprotein group were also decreased (fig. 3) . Concerning the characteristics of V H cl in ical course the dynamic follow-up of the serum immunoglobulins revealed the clinico-laboratory gravity to be atten­ded by a sharply expressed IgA increase (6) (fig. 4) . During the first 2—3 weeks after the onset of the illness there was a maximal IgM increase as an evidence for l iver cytolysis. A t the end of the icteric period IgG started an increase as a sign of fibrous-proliferative processes in l iver parenchyma. I n general, V H is characte-Dysproteinaemia in viral hepatitis 105 zed wi th an expressed gammopathy (a rising polyclonal immune response to the ntigen irritation) presented clearliest in the efferent stage of humoral immune esponse. Dysproteinaemia is best expressed in severe and dystrophic V H forms ) in which there is a strong reduction of synthesis proteins, of some immune /30 120 iW 180 30 so 70 60 50 40 30 I Щ Ш P i л хш\ vm\ \ ш 'А Л С L.M.H. С. L. М. И. С. L. М. Н. С L. М. Н. С L.M. Н. Си Со Fig . 5. Changes of complement components in different forms of v i ra l hepatitis esponse ones, and of three main classes of immunoproteins (fig. 5) . Glycocort i -coid treatment of V H causes an expressed negative effect on protein metabolism and plasma protein synthesis suppression, i . g. prealbumin, albumin, transferrin, a lpha r an t i t ryps in , ceruloplasmin and alpha 2-macroglobulin. Pr imary humoral immune response is also strongly inhibited and antibody production (mainly IgG and IgM) is markedly reduced. The presence and persistence of H B s A g induces a re­duction of the proteins of the three groups, too. The diagnostic significance of the individual proteins and immunoglobulins can be summarized as follows: They enable the differentiation between the A and В VH-forms by means of IgM dynamic follow-up, especially wi th posttransfusion hepatitis as wel l as be­tween the acute V H and chronic hepatitis where IgG levels are significantly higher. Both IgG and IgM are in normal ranges or slightly elevated only wi th choles­tatic V H forms and extrahepatic jaundices. The rapid and extreme increase of the three classes of immunoglobulins indicates the risk of an acute massive hepa­tic necrosis followed by a hepatic coma. The low levels of proteins of synthesis, especially of fibrinogen, give an evidence of a dangerous haemorrhagic diathesis in the course of the disease. IgM persistence in reconvalescent patients shows the danger of recidives. Serum proteins and immunoglobulins determination provides a better and more detailed and valuable information than proteinogram and colloid-stability hepatic tests for treating physicians. Various constellations of individual serum proteins and immunoglobulins are possible and can be applied for the evaluation of the functional state of the liver in V H . Bulgarian hydrolysate "Hydroprot" application (11) in the treatment of V H patients influences favourably the present dysproteinaemia by means of increas­ing the serum levels of the proteins of the first group (albumin, transferrin, hae-mopexin), of some ones of the second group (alpha 2-macroglobulin, alphai-easily sedimentating glycoprotein, group-specific protein, C 3-activator), e t c There is a simultaneous reduction of the serum level of the gamma-globulin fraction main­ly on the account of IgG. 106 M . Radkov R E F E R E N C E S 1. Б л ю г e p, А. Ф., В. Г. Й о н о в . Вирусный гепатит (болезнь Боткина), ч. I I , гл . 4, 242—246. — В: Основы гепатологии. Рига , 1975. — 2. К р ъ с т е в , З . , Т. I I I и п -к о в , А. М а л е е в . — В: Съвременни постижения в гастроентерологията. С , 1977, 40— 53. — З. М а л е е в , А., М. О г н я н о в . Д . Н и н о в а - Б р а д и с т и л о в а . Иму­нологични проблеми в гастроентерологията. С , Медицина и физкултура , 1978. — 4. О г ­н я н о в , М., Д . Н и н о в а - Б р а д и с т и л о в а . В: Наръчник по имунология на вът­решните болести. С , Медицина и физкултура, 1983. — 5. Р а д к о в , М. Съвр. проб л. инфекц. патол., 4, 1974, 21—31. — 6. Р а д к о в , М. Вътр. болести, 1973, № З, 58— 62. — 7. Р а д к о в , М. Епидемиол., микробиол. и инфекц. болести, 1973, № З, 240—244.— 8. Р а д к о в , М. В: Нац. конгр. заразни и паразит, болести, I V . Варна, 1976. Материа­ли. — 9. R a d k o v , М. Scr. sci. med., 13, 1976, 61—64. - 10. R a d k o v , M. Scr. set. med., 14, 1978, 107—112. — 11. R a d k o v , M. , T . G a n t c h e v a , P . M a n о 1 о v . I n : Sem. med. Balkan. , X V I . Bucuresti, 7—13. I X . 1980. — 12. S о d о m a n n , C. P . L a -bor. Blatter med. Diagn., 28, 1978, No 4, 148—154. ДИСПРОТЕИНЕМИЯ ПРИ ВИРУСНОМ ГЕПАТИТЕ M. Радков Р Е З Ю М Е Д л я изучения изменений белкового обмена и диспротеинемии при остром вирусном ге­патите было исследовано 554 больных и 112 выздаравливающих, лечившихся в клинике инфекционных болезней в Варне с 1970 по 1980 г. г. Иммунохимические исследования коли­чественных изменений индивидуальных сывороточных белков и исследования антител трех основных классов иммуноглобулинов показывают значительное уменьшение белков, что связано с белок-синтезирующей способностью печени (преальбумин, альбумин, трансферни, фибриноген, гемопексин). Большая часть белков в острой фазе воспалительного ответа т о ж е уменьшается (альфа 1 -антрипсин, альфа 2 -макроглобин, гаптоглобин, церулоплазмин). Уста­навливается повышение стоимости ИгА и нарастание тяжести заболевания. Автором подчеркивается факт, что определение сывороточных белков и иммуноглобу­линов дает детальную и ценную информацию о состоянии печени при заболевании гепатитом по сравнению с протеинограммой и коллоидостабилитетными печеночными пробами. 

DYSPROTEINAEMIA IN VIRAL HEPATITIS

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DYSPROTEINAEMIA IN VIRAL HEPATITIS

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