The Liver in Rheumatoid Arthritis
Authors: A. M. Lefkovits, I. J. Farrow
Journal: Annals of the Rheumatic Diseases (1955)

It is generally recognized that rheumatoid arthritis is a systemic disease characterized by profound and widespread disturbances in the con- nective tissues throughout the body, but having a special predilection for the periarticular and articular structures.Because the supporting framework of parenchymal organs is made up of connective tissue elements, it has been suspected that the function of these organs is altered in patients with rheumatoid arthritis as a result of direct involvement of the supporting framework and/or by secondary morpho- logical alterations of the parenchymatous elements.Thus, the liver has been the subject of investigation by several observers, and its function has been studied to determine whether this organ is involved in patients with rheumatoid arthritis.With the newer techniques of biopsy, liver tissue can be obtained with greater ease, so that the morphologic alterations in the liver may be studied and correlated with liver function tests in patients with various diseases.The purpose of this report is to present our experience with some laboratory procedures designed to test some of the functions of the liver in one hundred patients with rheumatoid arthritis, and to report the results of examination of liver tissue obtained by needle biopsy in twelve of these patients, and the post-mortem findings in the liver of an additional three of these patients.Review of the Literature A review of the existing literature relating to the involvement of the liver in rheumatoid arthritis reveals inadequate or contradictory information.Davis (1936) found a high incidence of increased levels of globulin and decreased levels of albumin in the plasma of patients with rheumatoid arthritis.The blood fibrinogen level was also found to be increased in these patients and there was an inverse relationship between the fibrinogen and globulin levels.Rawls and others (1937) used the azorubin S test as an index of liver function in one hundred patients who had "severe", "moderately severe", or "mild" rheumatoid arthritis: 27 of 34 severe cases (73 per cent.),21 of 44 moderately severe cases (47 5 per cent.), and seven of 22 mild cases (25 25 per cent.),amounting to 55 per cent. of the entire group, showed liver dysfunction.In addition, these authors also found a slight reduction of the serum proteins and a reversal of the A/G ratio in most of those cases (number not mentioned) that showed liver dys- function.They found no correlation between the dura- tion of the disease and impairment of liver function, but liver dysfunction was found more frequently in patients who had more severe rheumatoid arthritis.Rawls and others (1939) reported on the results of several liver function tests in fifty unselected cases of rheumatoid arthritis.The azorubin S test showed some evidence of liver dysfunction in 60 per cent.; the hippuric acid excretion (Quick method) was abnormal in 62 per cent.The bilirubin excretion (Soffer and Paulson method) was abnormal in twelve of 25 cases (48 per cent.); the galactose tolerance test (excretion of 2 g. or more) was abnormal in seven of 25 patients (14 per cent.); the icteric index (index 8 considered normal) was abnormal in 22 cases (44 per cent.); the serum albumin level was abnormal (4 g./100 ml. or less) in 34 cases (68 per cent.); the A/G ratio was abnormal (less than 2) in 38 cases (76 per cent.).The azorubin S test agreed more closely with the clinical evidence of liver damage than any other single test.Baggenstoss and Rosenberg (1943) reported on the post-mortem findings in thirty patients with rheumatoid arthritis whose death was due to various causes.The most frequently observed hepatic lesions were gross atrophy or hypertrophy, chronic passive congestion, fatty changes, "serous hepatitis", and central necrosis.These changes were associated with heart disease and/or inanition.They found no evidence to suggest that the reticulo-endothelial system was stimulated in these patients, nor did they find "any hepatic lesion which could be considered specific".Perlmann and Kaufman (1946) investigated the serum protein electrophoresis in 23 patients with rheumatoid arthritis.The results suggested an elevation of a globulins during the early course of the disease followed by a predominance in y globulins in later stages.Carter and Maclagan (1946) found the serum colloidal gold test to be positive in 76 per cent.and the thymol turbidity test to be positive in 38 per cent. of 34 patients with "atrophic type" of arthritis.Kalbak (1951) found positive thymol reactions in 75 per cent. of 21 patients with rheumatoid arthritis; 162 on July 20,