(Abstract.) By HERRMAN L. BLUMGART, M.D., AND (by invitation) HERBERT KATZIN, M.D., From the Medical Research Laboratories of the Beth Israel Hospital, and the Department of Medicine, Harvard Medical School, Boston. This investigation was aided by a grant from the DeLamar Mobile Research Fund. The term "cardiac cirrhosis" is used to denote various condi tions; according to some authors, the term signifies any type of hepatic fibrosis occurring in a cardiac patient; to others it signifies that the hepatic fibrosis is due to congestive failure, while some authors reserve the application of the term only to those cases in which cirrhosis of the liver due to congestive failure is responsible for clinical manifestations of portal obstruction. Thus, the varied usages of the term imply a simple co-existence of hepatic fibrosis and cardiac disease, a causal interrelationship between the two anatomic condi tions, or a causal morphological interrelationship which results in clinical manifestations of portal obstruction. These different connotations of the term have been responsible in part for the conflicting statements in the literature. There has also been considerable discussion as to the site and nature of the fibrosis in the liver, 'certain authors believing that this apparent fibrosis represents only a simple condensation of reticular fibers almost always confined to the centers of the lobules, whereas other investigators attribute the changes to active proliferation of fibroblasts. Con fronted in certain cases of congestive failure with the question of the presence of cardiac cirrhosis and with the paucity of pertinent avail able information, we undertook the following investigation of an un selected series of consecutive autopsied cases in order to learn: ( 1) the incidence of hepatic fibrosis in all cases with congestive heart failure; (2) the types and degrees of such hepatic fibrosis found in the cases of congestive failure of varying duration; (3) a comparison of these findings with those found in the cases without congestive fail- 82 "CARDIAC CIRRHOSIS" OF THE LIVER 83
ure ; (4) the incidence of hepatic fibrosis in patients with congestive
failure compared to that in patients with biliary tract disease. Such a comparison of the incidence and degrees of the various types of hepatic fibrosis in cardiac and non-cardiac cases should indi cate the significance of congestive failure as an etiological factor in causing cirrhosis of the liver. Two thousand consecutive autopsy protocols were examined, and the following three groups of cases were selected for further study in order to ascertain the interrelationship of chronic passive congestion, hepatic cirrhosis and certain other possible etiological factors in the production of this connective tissue increase. All cases in the series of 2000 showing chronic passive congestion, all those showing hepatic fibrosis, and all those showing disease of the biliary tract were placed in three separate groups. A study was made of the 95 cases in which chronic passive con gestion coexisted with cirrhosis, to ascertain the following facts: (1) the incidence of the types and extent of fibrosis; (2) the relation between the incidence of cirrhosis and the duration of congestive fail ure; (3) the relation between the degree of fibrosis and the duration of congestive failure; (4) the relation between the duration of failure and the presence, type and degree of fibrosis in the cases that showed predominant ascites; (5) the incidence of ascites, anemia and jaundice. It was evident that the incidence of fibrosis was higher in the cases with chronic passive congestion than in the entire unselected series; consequently it became of interest to ascertain whether mini mal changes in the liver were responsible for this finding. This did not prove to be the case.
DISCUSSION OF RESULTS.
Of patients dying with congestive heart failure, approximately
one-third showed increased hepatic fibrous tissue, which was twice the incidence found for the entire 2000 consecutive autopsies. The proportion of cases showing the various degrees of fibrosis was, in general, similar in the cases with and without congestive heart failure. Further, the incidence of fibrosis in patients with chronic passive congestion increased with the duration of failure, and the more severe grades were found in those patients in whom the illness was of longest 84 HERRMAN L. BLUMGART AND HERBERT KATlIN
duration. Thus, the causal significance of chronic passive congestion
in the production of hepatic fibrosis is emphasized by the increasing incidence and severity of the fibrosis with increasing duration of con gestive heart failure. The only type of fibrous tissue increase peculiar to this group of patients with cardiac decompensation was central fibrosis, for with one exception no instance of central fibrosis was found among the 1714 autopsies not showing congestive failure. . It should be noted that other types of fibrosis were also found in the cases with chronic passive congestion. Indeed, the incidence of each of the various kinds of fibrosis, except biliary, was higher in the group with congestive failure than in the remaining 1714 cases. Of particular interest was the finding of increased periportal connective tissue in 23 per cent of the 286 patients with congestive failure, as compared to 9 per cent in the 1714 cases without chronic passive con gestion. The occurrence of but two instances of biliary cirrhosis in the entire group of cases with chronic passive congestion indicates the absence of etiological relationship between these two conditions; two instances are within the expected incidence in 95 random autopsies. Since it is commonly accepted that diseases of the biliary tract are an important etiological factor in hepatic fibrosis, it was of in terest to learn that congestive failure is of comparable etiological significance. Clinical cardiac cirrhosis, signifying extreme fibrosis, which clearly results from chronic passive congestion and which causes evi dences of portal obstruction, does occur but is rare. Of the 286 cases with congestive failure there were only 15 cases which showed marked, but not necessarily predominant ascites requiring abdominal paracentesis. Six of these fifteen cases on autopsy examination showed cirrhosis of the type caused only by chronic passive conges tion, namely, central fibrosis. Although the majority of those who had failure one year or more showed increased fibrous tissue, they did not necessarily show preponderant ascites. The presence of anemia or jaundice in. congestive failure was not closely correlated with the postmortem finding of a pathological increase of connective tissue; these factors are consequently of no value in diagnosing hepatic cir rhosis clinically. "CARDIAC CIRRHOSIS" OF THE LIVER 8S
Morphological evidence of increased fibrosis of the liver was
seen in all of the six cases that had recurrent ascites, and were in fail ure two years or more. The clinical diagnosis of cardiac cirrhosis, signifying increased fibrous tissue in the liver, can be made, there fore, with considerable assurance in all cases of this type. If there is no marked portal obstruction, the fibrosis is not clinically important. From these studies, it would seem that cardiac cirrhosis signify ing morphological increase in connective tissue in the liver conse quent to congestive failure is present in approximately 50 per cent of all patients who have had congestive failure nine months or more. While central cirrhosis is characteristic of congestive failure and does not occur in patients with biliary tract disease, it would appear that other portions of the liver are also more susceptible to injury in patients with chronic passive congestion. Thus, 48 uncomplicated instances of periportal fibrosis were encountered in the group of 286 cases of chronic passive congestion, which contrasts with an expectan cy of but 30 cases if congestive failure were not a contributory factor. The occurrence of 17 additional cases in which definitely increased fibrosis of both the central and portal areas was found is further evi dence of an increased susceptibility of the portal areas to injury under such circumstances. Excluding the cases which showed increased connective tissue in both central and portal areas, the incidence of portal fibrosis in the 286 cases of congestive failure was 17 per cent, compared to an inci dence of central cirrhosis of 9 per cent in these cases. The significance of alcoholism as a contributory factor could not be accurately appraised, although increased consumption of alcohol was not appar ent in the records of the patients with congestive failure. From the foregoing evidence, the meaning of the term "cardiac cirrhosis" is clarified. In the morphological sense of increased fibrosis being due to chronic passive congestion, one may state that the majority of patients who have suffered from even mild congestive failure for 9 months or more show increased fibrosis of the liver, either central or portal, or a combination of both. Whether cardiac cirrhosis in the clinical sense of increased fibrosis causing clinical manifestations is present or not must be based on clinical evidence. If there is preponderant ascites, if there is marked elevation of the venous pressure but the liver is not palpable, 86 HERRMAN L. BLUMGART AND HERBERT KATZIN
and particularly if the spleen is palpable, clinical cardiac cirrhosis may
be assumed to exist. In a patient in whom the diagnosis of clinical cardiac cirrhosis is made, one may find portal or central fibrosis or a combination of these types, or diffuse patchy fibrosis. A reverse situation may be present in some patients, however. Even after the subsidence of the elevated venous pressure, the liver may be enlarged and ascites may be present. In such cases which represent an earlier stage of the one previously mentioned, the sinusoids are still dilated, increased fibrous tissue is present, and the surface of the liver is non tender and sometimes somewhat irregular.