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Infantile Cirrhosis of the Liver

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Infantile Cirrhosis of the Liver INFANTILE CIRRHOSIS OF THE LIVER P. KRISHNA RAO, B.SC., M.B.B.S., D.T.M. • H. (Eng.) (Pathologist, Victoria, Vani Vilas and Minta Hospitals, and Lecturer in Pathology and Bacteriology, University Medical School, Bangalore) Received July 16, 1941 CONTENTS PAGE INTRODUCTION .... 310 CLINICAL FEATURES .... 313 LABORATORY FINDINGS .. 314 MORBID ANATOMY AND HISTOLOGY 318 DISCUSSION .... 321 iEtiology .... 321 Type of Cirrhosis .... 326 Formation of Cirrhosis .. 332 SUMMARY .... 335 ACKNOWLEDGMENT .... 336 BIBLIOGRAPHY .... 337 Introduction PHYSICIANS and Pathologists in India have interested themselves in the study of the "Infantile Cirrhosis of the Liver" in view of the appalling mortality of the children claimed by this disease; yet our knowledge of the a~tiology and pathology of the disease is singularly defective. A case report by Sen in 1887 at the Calcutta Medical Association is, so far as I am aware, the first contribution to the literature on the subject, and he has described the disease as " a peculiar enlargement of the liver in young children only, both male and female, without any enlarge- ment of the spleen and associated with low fever, gradual emaciation, loss of appetite, sallow complexion and very slight jaundice, but not in all" In the discussion that followed the case report, Ghose, Coomer, Rakhaldas Ghose, Devendranath Dey, Bannerjee, Ahmed, Gibbons, Mcleod and Birch participated and the conclusions arrived at were as follows :-- (i) Infantile Cirrhosis of the liver was undoubtedly a peculiar disease found only amongst Indian children of the rich and the poor families alike. 310 Infantile Cirrhosis of tke Liver 311 (ii) The probable causative factors were the over-feeding of the children and bad hygenic conditions in which they were brought up. (iii) The enlargement of the liver was probably due to either amyloid or fatty degeneration. (iv) The pathology of the condition was doubtful and would remain so until the results of the careful post mortem examinations were available. In a leading article on "Hepatic Cirrhosis in Children" in the February issue of the Indian Medical Gazette of 1888, the following observations have been made :- "Is the disease, which has attracted attention in Calcutta, really Cirrhosis ? If so, what is its cause? Syphilis, struma, malaria, faulty hygienic or dietetic error, or some other undiscovered and unsuspected factor ? Does the disease occur elsewhere in Bengal or India ? If so under what circumstances and conditions ? ........ "The Calcutta Medical Society has pointed out a new and extensive interesting field of observation and study, and we trust that the observation will have the effect of attracting to it many workers and eliciting much light on what it must be confessed as still an obscure subject." The next notable contribution to our knowledge of the disease is that of Gibbons (1890). The credit of recording the post-mortem findings of the liver in this disease for the first time must go to Gibbons who in his classical report on four cases has given a most graphic account of the anatomy of the liver. Green Armytage (1926) published an elaborate paper on "Infantile Cirrhosis of the Liver ", wherein he attributed the condition in addition to the general defective deficient nature of food " to the lack of essential salts and endocrines in cow's milk on which the children were fed ". Considering the fact that the disease Infantile Cirrohosis is prevalent to a large extent in the Mysore State, the Government, impelled by their inherent desire to alleviate human suffering, created special facilities to carry out investigation regarding this disease. About 12 years ago Sankara Iyer of the Mysore Medical Service was specially deputed for conducting a survey on the prevalence of the disease in the State. In 1931 he published a report in which he mentioned that the distribution of the disease was confined to areas with a heavy rainfall; the worst affected parts being the districts of Kadur and Shimoga where the rainfall ranged from 80-145 inches and the less affected one being the Kolar District where the rainfall was less than 30 inches per year. 312 P. Krishna Rao Tirumurti and Radhakrishna Rao (1934) investigated 'Infantile Biliary Cirrhosis' cases and described three stages of the disease, viz., (i) the stage of onset, (ii) the stage of enlargement of the liver, and (iii) the stage of contraction of the liver. In a paper presented by me at the Mysore Medical Conference (1934) it was pointed out that B. coli was the probable causative factor for the production of cirrhosis. Subsequently in March (1935) at the next conference another paper was presented by me indicating that cow's milk and B. Coli were the mtiological factors and that the pathological condition of the liver was not that of biliary cirrhosis. The next landmark in the field of literature on the subject is the con- tribution made by Radhakrishna Rao (1935). In a most interesting report on the "Histopathology of the Liver in Infantile Biliary Cirrhosis" he has described the morbid anatomy of the liver. He has maintained that the morbid condition of the liver is not that of biliary cirrhosis, but is a " sub- acute toxic cirrhosis ". The value of this contribution is all the greater for the reason that it is the second of the kind in which an elaborate account of the morbid condition of the liver has appeared after a lapse of 45 years. Another noteworthy contribution is that of Lahiri (1936). He has shown that B. coli has a r61e in the mtiology of the disease, by isolating the organisms from the urine of the children suffering from the disease. Balasundaram (1940) has published a series of three papers: the first of which deals with the distribution of "Infantile Biliary Cirrhesis in India", the second with the " Soil and Environment ", and the third with the " Diet and Habits of Children " Several other publications have appeared from time to time and all these deal with the clinical features and the aXiology of the disease. Except- ing for one or two factors such as the occurrence of jaundice and the enlarge- ment of the spleen, all the investigators are agreed as to the signs and symptoms of the disease, but with regard to the causative factors of the disease there is yet great difference of opinion. In 1932 the task of conducting investigations regarding the disease was entrusted to me by the Government of Mysore. Since then, it was possible to study 105 cases, thanks to the co-operation of the medical men and women in the State who willingly referred the children suffering from this disease for my observation and treatment. P. Krishna Rao Proc. [~zd. Mcad. Sci., I~, vol. X/U, P1. X Male child Female child FIG. (a) Twins The female child being fed on cow's milk developed cirrhosis of the liver, whereas the male one being breast fed had no cirrhosis. FIG. (b) FIG. (c) Advanced case of cirrhosis of the liver with ascites An advanced case of Infantile Cirrhosis with and ~edema of hands and feet, hut no jaundice. jaundice and in a state of chol~emia P. Krishna Nao Proc. Ind. Mcad. Sci., B, val. )(IV, Pl. XI FIG. I Fie. 2 portion of the anterior surface of the right lobe of Cut surface of the liver showing lobulations. the liver. Note the nodular surface of the liver The surface is rough and granular (Case No. !). (Case No. 2). FIG. 3 FIG. 4 Anterior surface of the entire liver (Case No. 4). Posterior surface of the liver (Case No. 4). I~z/'antile Cirrhosis of the Liver 313 The present investigation was carried out on the following lines:-- (1) The study of clinical features, (2) Laboratory tests, (3)./Etiological factors, and (4) Post-mortem and histological examinations. In the present communication, a detailed account of the ~etiology, patho- logy and morbid anatomy of the liver, is offered in the hope that it will lead to a.,clearer understanding of the many obscure features of the Infantile Cirrhosis of the Liver. Clinical Features The disease is peculiar to children between the ages of 6 and 24 months, and the onset is either insidious or traceable to an attack of fever, broncho- pneumonia or severe diarrhoea. The child is observed to lose appetite and to become irritable. There is distension of the abdomen and the mother's attention is drawn to the peculiar offensive odour of the urine voided by the child. The child suffers from constipation. When the child is brought for examination and treatment the liver is observed to be enlarged, up to about two fingers' breadth, below the right costal margin; and the spleen is not palpable at this stage. The skin is dry and has a peculiar muddy appearance. In the course of 1 or 2 months after the onset of the disease, the liver is found to be enlarged up to the iliac crest on the right side, and up to about 2-3 fingers' breadth on the left side. On palpation it appears to be smooth and hard but not tender. Spleen may in some cases be found enlarged at this stage up to 1 or 2 fingers' breadth below the costal margin. In the course of another 2 or 3 months complications such as ascites, ~edema of the hands and feet, puffiness of the eye-lids and face set in (Fig. b, Plate X). The abdominal veins become prominent due to the establishment of the collateral circula- tion. At this stage the liver is seen to be slightly contracted. Jaundice may develop in a few cases in the late stages of the disease. The accompany- ing chart will indicate that jaundice is not an invariable sign of the disease and it is found to be absent in some cases where the liver is enlarged even up to the iliac crest.
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