Liver Cirrhosis

LIVER CIRRHOSIS (from the Greek cirrhos - reddish-yellow), a group of diseases characterized by a chronic diffuse lesion of the liver, changes in a number of other organs, and metabolic disorders. History. Cirrhosis is a term introduced in 1819 by Laennec. He used this term to designate a liver disease observed in a 47-year-old soldier in whom an autopsy revealed hemorrhagic pleurisy with ascites and a liver reduced to one-third its size, granular, and of a yellow or reddish color. The disease form itself, designated since then as cirrhosis, was known even earlier. As early as the 16th century, Vesalius and Fernel spoke of liver damage in alcoholics. In one of his letters, included in the treatise De sedibus et causis morborum, Morgagni gives a description of the disease in a Venetian senator who was fond of drinking; he had dyspepsia, abdominal enlargement accompanied by fluctuation, decreased urine output, edema of the lower extremities, and tremors, because of which physicians forbade the patient alcoholic beverages; at autopsy, a hard liver pierced with granulations and an enlarged spleen were discovered. The main sign by which liver diseases were subsequently classified as cirrhosis was the proliferation of connective tissue in this organ. Initially, the term cirrhosis was applied only to atrophic liver diseases. Later, it began to be used to designate certain forms of liver disease accompanied by an enlargement of this organ. One of the most striking descriptions of "hypertrophic cirrhosis" was given by Hanot in his well-known 1875 work. Soon after, Charcot and Gombault gave a classification of both forms of cirrhosis, "atrophic" and "hypertrophic," comparing their main features. The differentiation of cirrhosis formulated at that time has essentially served as the basis for both clinical and pathologoanatomical concepts in this field right up to the present time. Changes in the liver in individual forms of cirrhosis are quite diverse and are usually treated as chronic productive interstitial hepatitis. However, the most essential phenomenon in cirrhosis is considered to be the complex process of liver tissue restructuring occurring as a result of the interaction of three factors: an increase in the amount of intermediate connective tissue, dystrophy and death of liver cells, and regenerative changes. Changes in other organs and metabolic disturbances are partly the consequence of liver damage (ascites, jaundice) and partly develop as processes correlated with it (changes in the spleen and the rest of the hematopoietic system). A. Forms of liver cirrhosis. At present, there is no universally accepted classification of liver cirrhosis. Most existing classifications are based simultaneously on both etiological and anatomical factors; this includes in particular the most widespread subdivision of liver cirrhosis into atrophic, hypertrophic, biliary, and congestive. In 1929, Rössle made an attempt to provide a pathogenetic classification and subdivided all forms of cirrhosis into 5 types: 1. Histolytic cirrhoses, based on the epitheliotropic action of a poison and the development of hepatosis (degeneration of liver cells) followed by hepatitis (proliferation of interstitial connective tissue). 2. Angiohemotoxic or desmotoxic cirrhoses, based on the angio- and desmotropic action of a poison and the development of pure interstitial hepatitis. 3. Mixed forms. 4. Biliary cirrhoses, which are divided into holostatic, cholangitic, and cholangiotoxic (see below). 5. Rare forms of cirrhosis. This classification did not become widespread due to the difficulty of applying it in practice; subsequently, Rössle modified his classification, bringing it closer to the generally accepted one. Namely: 1. Laennec's atrophic cirrhosis. 2. Hypertrophic cirrhosis, with subdivision into: the hypertrophic form of Laennec's cirrhosis, fatty cirrhosis, the hypertrophic form of biliary cirrhosis (Hanot's cirrhosis), and hematotoxic, angiotoxic (pigmentary) cirrhosis. 4. Mixed forms. 5. Biliary cirrhoses. 6. Rare forms. However, even this subdivision, as Rössle himself points out, is still far from perfect. The various forms of liver cirrhosis are listed below in their most common presentation. 1. Laennec's cirrhosis (atrophic cirrhosis), the most frequent form of cirrhosis, is characterized by a dense, nodular liver; the latter is usually reduced, or more rarely, increased in volume, but there is no reason to distinguish between atrophic and hypertrophic forms of Laennec's cirrhosis: histological changes in both cases are identical. It is possible that these are merely separate stages of development of the same process. The surface of the liver is sharply granular (see separate plate, Fig. 2), and the parenchyma nodules protruding among the connective tissue retractions can be of various sizes; in most cases they are more or less uniformly small, less often large; however, there is no reason to distinguish between fine-nodular, coarse-nodular, and "smooth" forms of cirrhosis. On cross-section, the normal uniformly lobular pattern of the organ is replaced in cirrhosis by an irregular, often coarser, pseudolobular pattern, with the annular arrangement of connective tissue around areas of the parenchyma visible to the naked eye. The color of the organ varies: from yellowish-gray to brownish, depending on the amount of fat, blood, and bile pigments. Microscopically, the restructuring of liver tissue consists in the replacement of normal lobules by islets of liver parenchyma of various sizes and shapes. The lumen of the central vein in them is located eccentrically or is entirely indeterminate. These false lobules are partly remnants of normal lobules, partly islets of parenchyma newly formed through regeneration. The latter exhibit partly atrophic and various dystrophic changes, and partly, conversely, their cells are hypertrophied. Between the false lobules (often also growing into them) lies newly formed connective tissue with varying content of vessels and cells, surrounding the pseudolobular islets of liver tissue in a ring-like manner (hence the name "annular" cirrhosis). The ingrowth of connective tissue inside the lobules in atrophic cirrhosis is usually mild. Initially, reticular fibers develop, which then turn into collagenous fibers. Kupffer cells play a major role in the proliferation of cellular elements. Lymphoid infiltrates, expressed to varying degrees, are frequently encountered. In the layers of overgrown connective tissue, newly formed tubular bile ducts are usually found in varying quantities. Strands of atrophic liver cells resembling bile ducts (false bile ducts) are also located here. Formerly, regenerative significance was attributed to the proliferation of bile ducts, thinking that liver cells originate from them. At present, these pictures are attributed to false bile ducts. Vessels in the overgrown connective tissue often have fibro-hyalinized and thickened walls. Other main changes in Laennec's cirrhosis consist of ascites and splenomegaly; however, ascites is inconstant (figures given by authors range from 30% to 65%). Enlargement of the spleen is also inconstant (occurring according to various statistics in approximately 53–93% of cases) and usually does not reach a large degree. The spleen is dense, often with a thickened capsule, marked development of the stroma, and wide sinuses. Sometimes atrophic cirrhosis is accompanied by jaundice (in approximately 20–30% of cases). Especially characteristic of it are phenomena of venous stasis in the portal system with dilatation of collateral veins (see Caput medusae), including esophageal veins (not infrequently with fatal bleeding from them) (on collaterals in liver cirrhosis, see below). Sometimes sclerosis and thrombosis of the portal vein are observed. 2. Fatty cirrhosis—of the atrophic type, but with marked large-droplet fatty degeneration of liver cells. Many do not isolate fatty cirrhosis into a separate form, since any atrophic cirrhosis features more or less marked fatty degeneration of liver cells. In cases of marked primary fatty degeneration of the liver (in alcoholism, tuberculosis), some increase in the amount of interstitial tissue is also frequently found, albeit mainly due to reticular fibers (Gitterfaserncirrhose). 3. Pigmentary cirrhosis differs from atrophic cirrhosis in the liver picture only by a particularly sharp accumulation of hemosiderin, giving the liver a rusty hue (a certain amount of hemosiderin is constantly found in the liver even in atrophic cirrhosis). The pigment is deposited in liver and Kupffer cells, as well as in the interlobular connective tissue. Usually, in pigmentary cirrhosis, there is hemochromatosis or hemosiderosis (see) of other organs as well. Therefore, it is more correct in such cases to speak of a general disorder of pigment metabolism accompanied by liver cirrhosis. Not infrequently, cirrhosis of the pancreas with symptoms of diabetes is observed simultaneously (see Hemochromatosis). The nature of the relationship between pigmentary disturbance and liver cirrhosis has not been elucidated. 4. Biliary cirrhoses are of two types: ordinary cholangitic cirrhosis and Hanot's hypertrophic cirrhosis.

The development of cirrhotic changes on the basis of a single prolonged stagnation of bile is also possible (cholostatic cirrhosis), but is observed very rarely; usually, cholangitis is present simultaneously. a) Ordinary cholangitic liver cirrhosis is associated with chronic inflammation of the bile ducts and prolonged jaundice, which causes small foci of necrosis in the hepatic tissue. The proliferation of connective tissue proceeds between the lobules along the course of the bile ducts, as well as within the lobules. The liver retains its size or is somewhat diminished and hardened; its surface is usually smooth; on cross-section, the tissue has an indistinctly annular pattern and is strongly icteric. b) Hanot's cirrhosis (hypertrophic cirrhosis) is rare. Formerly, this type of cirrhosis, in accordance with the description given to it by Hanot, was considered an independent disease form and was regarded as hypertrophic Hanot's cirrhosis alongside Laennec's atrophic cirrhosis. Some classified it as a typical example of a primary hepato-lienal disease; Rössle classified it as a primary productive hepatitis. Subsequently, however, it became clear that under the name of Hanot's hypertrophic cirrhosis

Figure 1. Liver cirrhosis: a - capsule; b - cirrhotically altered parts; c - hypertrophic parts of the parenchyma; d - dilated branches of the portal vein. Figure 2. Granular liver. Figure 3. Fresh choroiditis. Figure 4. Disseminated choroiditis.

the most diverse types of liver cirrhosis in terms of origin were described, and most often those associated with lesions of the bile ducts. In this connection, doubts arose as to the necessity of singling out Hanot's cirrhosis as an independent nosological entity (Rössle, Fissinger, de Jong); the majority began to classify it among cholangitic liver cirrhosis. This form of liver cirrhosis is characterized by enlargement (sometimes very significant) and hardening of the liver; the liver surface is smooth. On cross-section, the usual liver pattern or annularity is not noticeable (see separate plate, Fig. 1); the cut surface is smooth, brownish-green (from jaundice). Under the microscope, there is a diffuse proliferation of cell-rich connective tissue, which is located not only between the lobules but also within the lobules, separating individual hepatic cells and groups of them from each other (insular or island-like proliferation of connective tissue). The spleen is sharply enlarged, jaundice is present (without stool discoloration); ascites is usually absent. The origin of jaundice is explained in various ways: by compression of small bile ducts by the proliferated connective tissue, degeneration of hepatic cells, and a general disturbance in the production of bile pigments both in the liver itself and outside it. 5. Cirrhosis in Banti's disease does not differ in its liver picture from atrophic cirrhosis. For other features, see Banti's disease. 6. Liver cirrhosis after acute yellow atrophy in protracted forms of the latter is characterized by particularly sharp phenomena of regeneration in the form of numerous, partly large nodes, mostly yellow in color, delimited by fibrous tissue. Only those cases can be attributed to the group of liver cirrhosis where the process proceeds more or less diffusely and the nodes of the regenerated parenchyma are distributed evenly throughout the liver among the fibrous tissue. However, even these cases differ from the picture of atrophic cirrhosis: the nodes of hepatic tissue in them are always larger and softer, the connective tissue forms coarse layers around them without producing more diffuse proliferations, the structure of the normal liver is better expressed in the parenchyma nodes, and the phenomena of tissue restructuring of the organ are scarcely noticeable. In contrast to atrophic cirrhosis, jaundice as well as enlargement of the spleen in this form are observed as a rule. The inclusion of the latter in liver cirrhosis is generally based only on the external similarity of liver changes in some cases with atrophic cirrhosis; however, the course and character of the process in the one and the other case are completely different. 7. Cardiac cirrhosis (cirrhose cardiaque) is sometimes the name given to severe degrees of cyanotic induration of the liver (see Liver, pathological anatomy) in venous congestion, mostly on the basis of right-heart failure. The liver is reduced, dense, slightly bumpy, its acinous structure is disrupted, the peripheral parts of the lobules, surrounded by congested fields, give a pseudolobular pattern. The amount of connective tissue between the lobules and within them is increased, regeneration areas are encountered, although weakly expressed. This form can be attributed to liver cirrhosis only by the external similarity of liver changes, but by origin and development it should essentially be removed from the group of cirrhoses. 8. Tuberculous cirrhosis, arising on the basis of scarring of multiple tubercular foci in the liver, is very rare. Sometimes tuberculosis merely joins the liver cirrhosis in the form of miliary tubercles (often simultaneously with tubercular peritonitis). Frequently also in pulmonary tuberculosis, marked fatty degeneration of the liver is observed with weak secondary cirrhotic changes. There is no reason to speak of tubercular liver cirrhosis on the basis of the presumed etiological significance of tuberculosis in it; recent statistical data (Shlapobersky, de Jong) speak in favor of the absence of a connection between tuberculosis and cirrhosis. 9. Syphilitic cirrhosis is sometimes the name given to liver changes in both congenital and acquired syphilis (see Liver), but such a designation is essentially incorrect, especially in relation to acquired syphilis, in view of the clearly expressed focal nature of the changes it causes in the liver ("focal" liver cirrhosis). One could also speak of syphilitic liver cirrhosis in cases of the development of vulgar atrophic cirrhosis in syphilitics, which happens frequently (in de Jong's series, in 35 cases out of 200). However, it is difficult to say whether syphilis has the significance of an etiological moment in these cases or whether other factors (salvarsan, alcoholism) participate here. 10. Malarial cirrhosis is similar to atrophic cirrhosis, characterized by abundant deposition of malarial pigment, mainly in Kupffer cells (see Malaria, pathological anatomy). 11. Zooparasitic cirrhoses are caused most frequently by certain flukes, especially Clonorchis (Opisthorchis) felineus and schistosomes (Schistosoma haematobium, Mansoni, japonicum), and are encountered almost exclusively in Japan and in certain tropical countries (Surinam, Guiana, East Indies). Inflammatory changes usually have a focal character, localizing near accumulations of parasites, and therefore do not properly belong to the group of cirrhoses. 12. Cirrhosis in Wilson's disease and in pseudosclerosis (see Westphal-Strümpell disease, Wilson's disease). 13. Cirrhoses in childhood are of various types: syphilitic ones are most frequent, others are very rare (1-2% of all cirrhosis cases), have the appearance of atrophic cirrhoses, rather coarsely granular; they are usually accompanied by enlargement of the spleen and jaundice, and sometimes also by hemorrhagic diathesis. Apparently, in a number of cases, one is dealing with a primary hepato-lienal disease (Moon, de Jong). Regarding Pick's pericarditic pseudocirrhosis of the liver, see Glazed organs, Perihepatitis, Polyserositis. B. The etiology and pathogenesis of some forms of liver cirrhosis are sufficiently elucidated (syphilitic, malarial, cholangitic, etc.). The most difficult and important question is the origin of vulgar atrophic cirrhosis as the most frequent form (up to 90% of all forms of cirrhosis). The long-standing debate as to whether liver cirrhosis originates from a primary lesion of the liver parenchyma or a primary proliferation of connective tissue still continues. However, at the present time this debate has lost its sharpness; there is an increasing conviction that liver cirrhosis (of non-specific origin) arises as a result of the chronic action of toxic or infectious agents that damage all functional elements of the liver; as a result, repair occurs