PAPERS for the Original Department should be in hand one month in advance, and contributed to THE MEDICAL FORTNIGHTLY exclusively. A liberal number of extra copies will be furnished authors, and reprints may be obtained at reasonable rates, if request accompanies the manuscript. Engravings from photographs furnished free. Contributions, and books for review, should be sent to the Editors, 312 Century Building, St. Louis. COLLABORATORS. ALBERT ABRAMS, M. D., San Francisco. RICHARD T. HEWLETT, M. D., London, Eng. HOBART A. HARE, M. D., Philadelphia. H. M. WHELPLEY, M. D., St. Louis. The Classification of Cirrhosis of the Liver. BY ARTHUR R. EDWARDS, A. M., M. D., CHICAGO, Professor of Principles and Practice of Medicine and Clinical Medicine, Northwestern University Medical School; Attending Physician to Cook County, Mercy, Wesley. St. Luke's Hospitals, etc. Read at Symposium on Cirrhosis of the Liver before a joint meeting of the Chicago Medical Society and the Chicago Society for Internal Medicine, January 29, 1902. A CLASSIFICATION of hepatic cirrhosis may be made upon an etiologic, pathologic, or clinic basis. Schematism and over-refinement is often observed in the classifications made, yet it is difficult to formulate a division to include all varieties without some contradictions, either pathologic or symptomatic. Accurate theoretic and pathologic differentiation is important with reference to the therapy, as in syphilitic cirrhosis, in malaria, gout, diabetes, dyspepsia, lead poisoning, or other kindred causes, and again in atrophic cirrhosis in the relief of which surgery now plays a constantly increasing role. (I) Important as is the recognition of the etiologic factor, clinic confusions arise, if classifications be made on this basis alone. Thus, for example, alcohol or tuberculosis may produce the fatty cirrhosis, or an atrophic cirrhosis may result from several causes, as alcoholism, syphilis and malaria. Chauffard, in Charcot's Traite de Medicine, gives the following excellent anatomic and etiologic classification: (1).—VASCULAR CIRRHOSIS. (a) toxic (1) by extrinsic poisons. (2) by intrinsic poisons. (b) infective (1) direct microbic infection. (c) dystrophic (1) arterio-sclerotic. (2) passive congestion. (III). CAPSULAR CIRRHOSIS. (a) by chronic localized perihepatitis. (b) by chronic generalized peritonitis. (The letters indicate the etiologic, and the Roman numerals the pathologic classification.) (II). THE PATHOLOGIC CLASSIFICATION. 1. Distribution of Connective Tissue. This point is the most confusing of any connected with the differential pathology. Charcot drew such sharp lines between the different forms that, as Rosenstein has said, one would conclude that a glance through the micro scope would readily differentiate them. Charcot described: 1. Cirrhose d'origine biliare. 2. Cirrhose d'origine veineuse. 3. Cirrhose monocellulaire, characterized by the presence of connective tissue between individual cells within the lobule, seen especially in hereditary syphilis. The French school postulates the following differentia between the two types of cirrhosis; in the venous variety, the connective tissue and inflammation extend around several lobules, sending connective tissue processes late if at all, into the lobule, hence a peripylephlebitis; in the biliary type, the connective tissue begins in the lobule, around the smaller bile radicles, with increase in the biliary vessels, hence a primary angiocholitis or periangiocholitis. In the venous form, the connective tissue exerts compression upon the lobule en masse, hence called cirrhose multilobulaire s. annulaire; in biliary cirrhosis, the compression is in the lobule, hence denominated cirrhose insulaire s. monolobulaire. In the vulgar cirrhosis, the process is extralobular; in biliary it is extra- and intralobular. In the venous or portal type the liver is small, ascites is present, there is no icterus and the liver cells are degenerated; in the biliary form the liver is large, ascites and other expressions of stasis are absent, icterus is the cardinal symptom and the liver cells are intact a pathognomonic criterion. Rosenstein rejects Charcot's and Hanot's terms, "intra- and extralobular", "multi-and monolobular", and asserts that there is no cirrhosis in which there are not now some small lobules surrounded by connective tissue, and again many acini surrounded by connective tissue. Both distributions may occur in a single liver. In the annular and insular forms Rosenstein finds an actual histologic differential point, and the concentric ensnaring of smaller or larger groups of lobules in cases of Laennec's cirrhosis are to him and Ackermann truly distinctive. In typical hypertrophic cirrhosis the connective tissue sends out processes into and around the lobules, now surrounding an entire lobule, now only certain cell groups. Rosenstein, Kelsch, and Wannebroecq certainly overdraw the situation in saying that nearly all cirrhoses are mixed types (Type mixte. of Dieulafoy 20 and Guiter 21. See also references, 22, 23, 24,). Orth (25) refuses to divide cirrhosis into different types upon the distribution of connective tissue in regard to the lobule. When said tissue seems to surround lobules, the appearance is usually accidental. The same liver may show multilobular isles, large and small monolobular isles. Regarding the relation between parenchyma and interstitium, the same specimen may show here a sharp distinction and elsewhere the connective tissue running into the lobules Orth regards all cirrhoses as essentially the same process. Hamilton also thinks Charcot's and Gombault's views exteme. Brieger (26) and Sabourin (27) affirm that the connective tissue begins in the hepatic vein zone. French authors find the connective tissue around the bile vessels, the veins being involved later and to a less extent. Hamilton says the secondary connective tissue bands in the lobule are more numerous in biliary than in atrophic cirrhosis. (2) The Bile Ducts.-In general, the French authors describe a hyperplasia of the biliary passages in biliary cirrhosis. Brieger finds in every circumscript connective tissue formation in the liver an increase in the bile vessels in tuberculosis, carcinoma, adenoma, gregarinae, distomata, and even in corset liver. Rosenstein states that he has found them (perhaps by accident) more frequently in atrophic than in biliary cirrhosis and cannot, therefore, consider them pathognomonic of biliary cirrhosis; also that they sustain no causal relation to icterus. The ducts are described as filled with degenerated and desquamated epithelium and less frequently with pigment masses. Rosenstein affirms the existence of this condition in the hypertrophic cirrhosis without icterus. Ackermaun (28) thinks the new formed bile vessels communicate with the smallest biliary vessels on the one hand, and with the main duct on the other, and gives as proof the results of artificial phosphorus cirrhosis. Orth considers the canal system as due, chiefly at least, to atrophic liver cells arranged in rows, although he admits they may in part be neoplastic. They can be injected from the biliary system, and are absent in no type of cirrhosis. (Also the view of Kelsch, Kiener, Sabourin.) Friedlander (29) was the first to discover this reversion of atrophic liver cells to their embryonal duct-like condition. The ducts disappear where the connective tissue is densest. According to Price (30) the ducts are of two kinds: 1, true bile ducts; 2, duct-like structures continuous with and imbedded in large tracts of fibro-nucleated tissue, being transformed into fibrous tissue. Small nodules on the surface are occasionally due to biliary polyadenomata (31). Ziegler describes a bile vessel proliferation in all cirrhoses. In biliary cirrhosis proper, the prime and initial lesion is an ascending infection from the intestines which induces by its moderate yet con stant irritation an interlobar desquamative obliterative angiocholitis followed by hypertrophy of the liver cells, polycholia, and connective tissue formation. (3) Character of the new-formed Connective tissue.-Ackermann calls attention to the fact that the new-formed connective tissue in biliary cirrhosis remains uncontracted, hence the names elephantiasis hepatis (Eichorst) and L'hypermegalie (Schachmann.) In atrophic cirrhosis it is fibrous; in hypertropic embryonal in character (Rosenstein.) Stadelmann remarks that the biliary cirrhotic liver never contracts. Orth admits that a biliary form exists, characterized by its clinical course and lack of atrophy, with the qualifying phrase that the future only can assign to biliary cirrhosis its exact status. Strumpell thinks the lack of contraction has been overestimated and that the organ would contract, were life protracted Hamilton describes the connective tissue bands as finer in hypertrophic than in atrophic cirhosis. (4) Condition of the Liver Cells.-That the liver cells preserve their form and integrity is characteristic of biliary cirrhosis. They are at most only flattened at the periphery of the lobule and may disappear. Fatty infiltration and necrosis is said to be very rare. The nuclei are preserved. The cells are sometimes pigmented or atrophied, but often both cell and nucleus hypertrophy and divide. In Laennec's form the cells are often degenerated, very frequently fatty, now in the center, now in the periphery of the lobule. Hamilton says fatty degeneration is rare even in Laennec's cirrhosis, while fatty infiltration and hypertrophy occur. According to Schachmann, Hanot's cirrhosis is distinguished even from biliary obstructive cirrhosis by the hypertrophy of the liver cells whose cell activity is increased (polycholia, diabete biliare). (5) Condition of the Blood Vessels.-The interlobular blood vessels in the portal cirrhosis are diseased, while free in the biliary type (Rosenstein). The integrity of the hepatic or sublobular system is, according to Jaccoud (32) quite exceptional. Ackermann distinguishes an atrophic cirrhosis (Laennec's) in which the cells die first, and are replaced by connective tissue. According to him, Laennec's cirrhosis and one variety of large cirrhotic liver are the same, for in certain livers some parts are atrophic and others again are hypertrophic. Ackermann admits the identity of the French hypertrophic variety, which has, he states, nothing in common with the atrophic cirrhosis except the connective tissue proliferation. It is apparently a primary connective tissue hypertropy with consequent atrophy of the liver cells, a hypertrophy occurring around the interacinous blood vessels, never leading to characteristic granulations, producing moderate, or no stasis, i. e., scanty ascites and insignificant splenic tumor and occuring also in horses, fowls, and cattle, while the atrophic is seen in man only. The difference between this form and Charcot's description is obvious. (III). THE CLINIC CLASSIFICATION.-DEFINITION OF TERM "HYPERTROPHIC. Hamilton takes exception to the term "hypertrophy," arguing that an enlarged liver may be very atrophic. Liebermeister considers that the terms "biliary" and "hypertrophic" are not identical, nor are venous and atrophic cirrhoses one. The portal vein form usually shrinks and the biliary form usually enlarges, but exceptions occur, as 1, portal vein forms remaining large till death; or 2, biliary types atrophying to a certain degree. Most writers, e. g. Strumpell, regard "biliary" and "hypertrophic" as synonymous, and "venous" and "atophic" as the same. The hypertrophic, alcoholic cirrhosis of Hanot and Gilbert (18) is characterized by edges less sharp than normal; red or brown color: surface furrowed by uneven areas, varying in size, the unevenness being less than in the atrophic form; by granulations on the surface, by enlarged spleen, ascites, collateral circulation, etc. They assert there are many transitional forms between it and the atrophic alcoholic cirrhosis, so that great importance does not attach to size alone. Recovery occurs in this more than in any other form. Laennec seems to have known but one type of cirrhosis. Hanot supported by Hayem, Cornil and Charcot insisted even more than did Todd upon the divorce of hypertrophic and atrophic cirrhoses. This separation of the two forms is the constant theme of the French school, but they do not seem concerned as to whether an enlarged liver may become small. Cornil (19) was the first to discover in the hypertrophic form, a very rich network of bile vessels, and upon this Hanot based his clinical division of cirrhoses into, 1, the venous; and 2, the biliary. Litten and Mangelsdorf sought to show that biliary was but the first stage of the vulgar cirrhosis plus icterus. In Germany, the different cirrhoses are largely held to be mere variations of a single fundamental cirrhosis. Stadelmann 11 voices this opinion when he can not find a difference between the two forms for the following reasons: 1, there is a hypertrophic cirrhosis without icterus; 2, hypertrophic cirrhosis can later atrophy; 3, icterus can be very marked in Laennec's cirrhosis. It seems to us that undue stress has been placed on size alone. An enlarged cirrhotic liver is by no means a hypertrophic cirrhosis. A consideration of the possibillity that the vulgar hepatic cirrhosis may be preceded by hypertrophy, is pre-requsite. Todd 1 claims that there is never preliminary enlargement in Laennec's cirrhosis, and he was unable to find in literature a reliable instance of a hypertrophic passing into an atrophic cirrhosis. Stricker (Traube's clinic) observed livers shrink to half their former length in one month. Therefore subacute and acute hepatitis must be excluded. Rosenstein 2 and Labadie Lagrave 3 agree with Todd. Bright 4, Budd 5, Saunders and Frerichs 6 have said that contraction is occasionally antedated by a stage of enlargement. Murchison's 7 experience taught that in a considerable proportion of cases of cirrhosis, the liver is still very much enlarged, often from fat, after symptoms of portal obstruction have set in, and that patients often die in this stage with jaundice, hemorrhage and symptoms of blood poisoning. Leudet 8, from a pathologic standpoint comes to the conclusion that increase in |