Scand J Rheumatology 5: 6 5 4 9 , 1976
MORPHOLOGICAL CHANGES IN LIVER BIOPSIES FROM PATIENTS WITH RHEUMATOID ARTHRITIS Odd Dietrichson, Arne From, Per Christoffersen and Erik Juhl
Scand J Rheumatol Downloaded from informahealthcare.com by Mcgill University on 12/16/14 For personal use only.
From the Medical Department 2 , Department of Physical Medicine, and Department of Pathology, Kommunehospitalet, Copenhagen, Denmark
ABSTRACT. Oxyphenisatin is known to induce liver damage and is suspected to cause or perpetuate chronic liver disease. In order to evaluate the hepatotoxic effect of longterm therapy with oxyphenisatin 26 consecutive patients with rheumatoid arthritis were investigated for the presence of liver disease. In all cases, liver biopsy, biochemical Uver function tests and determination of Hepatitis-B antigen were performed. Ten patients showed no pathological changes in the Uver biopsy and a further 2 had only non-specific changes. Seven patients had fatty liver, 5 passive congestion, one haemosiderosis and only one had cirrhosis of the Uver. No correlation was found between the activity of rheumatoid arthritis, the duration of the disease, the drug therapy given, and the liver damage.
Rheumatoid arthritis (RA) is a systemic disease of which the arthritis is but a single manifestation. Thus, involvement of visceral organs occurs, and especially involvement of the heart (2) and amyloid degeneration in different organs (22). Morphological and functional changes in the liver are also described (11, 13, 18, 19, 21), but it is uncertain whether these are actually part of the disease or are caused by the medical therapy. In Denmark the laxative, oxyphenisatin acetate is employed in combination with the popular codeine-containing analgesics (7). Oxyphenisatin has proved to have a hepatotoxic effect and may well cause acute o r perpetuate chronic liver damage
patients included in this prospective study fulfilled the criteria for definite or classical RA put foward by the American Rheumatism Association ( I ) . The patients were questioned closely about the course and duration of the disease, medical treatment, other diseases previous or present, and alcohol consumption. The activity of the rheumatic disease was estimated by the sedimentation rate (SR) and determination of rheumatoid factors, using both latex particles sensitized with human gammaglobulin (Hyland reagent) and the sheep cell agglutination test (Waaler-Rose). These reactions and the LE-cell test were performed by routine methods at Statens Seruminstitut, Copenhagen. Biochemical liver function tests including aspartate aminotransferase, alkaline phosphatase, bilirubin, prothrombin-proconvertip and albumin, were camed out by conventional methods. Hepatitis-B antigen (HB-Ag) in serum was demonstrated by immunoelectro-osmophoresis according to the method described by Prince &Burke (17). The liver biopsies were performed according to the technique of Menghini. The tissue was fixed in formalin, embedded in paraffin, and cut into 51 serial sections of 6 Pm * The assessment was performed on haematoxylin-eosin and v. Gieson-Hansen stained preparations by one of the authors (P. C.) without knowledge of the clinical data. Further sections stained for reticulum fibres (9), iron (16), amyloid (8) and pyroninophil substance (3) were available from all biopsies.
(20).
Table I. Histological diagnosis based on liver biopsies from 26 patients with rheumatoid arthritis
The present paper describes the morphological changes found in liver biopsies from consecutive patients with RA, and correlates these findings with the medical treatment.
Histological diagnosis
MATERIAL A N D METHODS The material comprised 26 consecutive patients (I9 women and 7 men) aged 16-78 years admitted to the Dept. of Physical Medicine, Kommunehospitalet, Copenhagen. All 5-761866
Cirrhosis Fatty liver Haemosiderosis Passive congestion Non-specific changes No pathological changes
Number of biopsies
1 7 1 5 2 10 26
%
4 21 4 19 8
38
I00
Scand J Rheumatology 5
66
0 .Dietrichson et al.
Scand J Rheumatol Downloaded from informahealthcare.com by Mcgill University on 12/16/14 For personal use only.
Table 11. Clinical and serological data, results of biochemical liver function tests, and diagnosis based on liver biopsies from 26 patients with rheumatoid arthritis
Patient
Sex
Age (y.)
J. F.
F
72
K. E. G. K. G. C.
M F F
73 40 61
T. M. B. H. M. H. I. H. L. H.
F F F F M
50 64 57 67 71
M. E.
F
72
A.B. A. P.
M F
36 69
K. L. K. F. E. V.J.
E.V.V 0.N.
F M M F F
16 78 63 57 66
M. P. A. J. I. H. J. A. 0.J. E. L. K. S. K. A. E. J.
F F F M F M F F F
77 61 59 38 69 57 73 40 68
Other diseases, previous or present Liver disease for 10 years Asthma
Duration ofRA (Y.)
Series with gold
Steroid
10
1
10 y ,
21 8 9
2 4 3
34 9 20 6
6 4 1 2 0
1953-58 5 mo. 1964+ 1973 19 y. 9 Y. 0 0 1968-70
23
4
0
20 y.
64
25 7
3 I
0 0
? 1 Y.
24 87
0
9
1 0 1 1 2
0 0 0 0 1964-73
1 0 ? 6 Y. 11 y.
124 40 30 50 80
0
0 2 0 1 7 4 1 9 1
0 0 0 0 11 y. 1956-69 0 5 Y. 0
3 Y.
70 41 38 15 9 34 56 15 30
0
If
Cancer recti; alcoholism Diabetes; heart disease Myxoedema; heart disease
MORPHOLOGICAL CHANGES IN LIVER BIOPSIES FROM PATIENTS WITH RHEUMATOID ARTHRITIS Odd Dietrichson, Arne From, Per Christoffersen and Erik Juhl
Scand J Rheumatol Downloaded from informahealthcare.com by Mcgill University on 12/16/14 For personal use only.
From the Medical Department 2 , Department of Physical Medicine, and Department of Pathology, Kommunehospitalet, Copenhagen, Denmark
ABSTRACT. Oxyphenisatin is known to induce liver damage and is suspected to cause or perpetuate chronic liver disease. In order to evaluate the hepatotoxic effect of longterm therapy with oxyphenisatin 26 consecutive patients with rheumatoid arthritis were investigated for the presence of liver disease. In all cases, liver biopsy, biochemical Uver function tests and determination of Hepatitis-B antigen were performed. Ten patients showed no pathological changes in the Uver biopsy and a further 2 had only non-specific changes. Seven patients had fatty liver, 5 passive congestion, one haemosiderosis and only one had cirrhosis of the Uver. No correlation was found between the activity of rheumatoid arthritis, the duration of the disease, the drug therapy given, and the liver damage.
Rheumatoid arthritis (RA) is a systemic disease of which the arthritis is but a single manifestation. Thus, involvement of visceral organs occurs, and especially involvement of the heart (2) and amyloid degeneration in different organs (22). Morphological and functional changes in the liver are also described (11, 13, 18, 19, 21), but it is uncertain whether these are actually part of the disease or are caused by the medical therapy. In Denmark the laxative, oxyphenisatin acetate is employed in combination with the popular codeine-containing analgesics (7). Oxyphenisatin has proved to have a hepatotoxic effect and may well cause acute o r perpetuate chronic liver damage
patients included in this prospective study fulfilled the criteria for definite or classical RA put foward by the American Rheumatism Association ( I ) . The patients were questioned closely about the course and duration of the disease, medical treatment, other diseases previous or present, and alcohol consumption. The activity of the rheumatic disease was estimated by the sedimentation rate (SR) and determination of rheumatoid factors, using both latex particles sensitized with human gammaglobulin (Hyland reagent) and the sheep cell agglutination test (Waaler-Rose). These reactions and the LE-cell test were performed by routine methods at Statens Seruminstitut, Copenhagen. Biochemical liver function tests including aspartate aminotransferase, alkaline phosphatase, bilirubin, prothrombin-proconvertip and albumin, were camed out by conventional methods. Hepatitis-B antigen (HB-Ag) in serum was demonstrated by immunoelectro-osmophoresis according to the method described by Prince &Burke (17). The liver biopsies were performed according to the technique of Menghini. The tissue was fixed in formalin, embedded in paraffin, and cut into 51 serial sections of 6 Pm * The assessment was performed on haematoxylin-eosin and v. Gieson-Hansen stained preparations by one of the authors (P. C.) without knowledge of the clinical data. Further sections stained for reticulum fibres (9), iron (16), amyloid (8) and pyroninophil substance (3) were available from all biopsies.
(20).
Table I. Histological diagnosis based on liver biopsies from 26 patients with rheumatoid arthritis
The present paper describes the morphological changes found in liver biopsies from consecutive patients with RA, and correlates these findings with the medical treatment.
Histological diagnosis
MATERIAL A N D METHODS The material comprised 26 consecutive patients (I9 women and 7 men) aged 16-78 years admitted to the Dept. of Physical Medicine, Kommunehospitalet, Copenhagen. All 5-761866
Cirrhosis Fatty liver Haemosiderosis Passive congestion Non-specific changes No pathological changes
Number of biopsies
1 7 1 5 2 10 26
%
4 21 4 19 8
38
I00
Scand J Rheumatology 5
66
0 .Dietrichson et al.
Scand J Rheumatol Downloaded from informahealthcare.com by Mcgill University on 12/16/14 For personal use only.
Table 11. Clinical and serological data, results of biochemical liver function tests, and diagnosis based on liver biopsies from 26 patients with rheumatoid arthritis
Patient
Sex
Age (y.)
J. F.
F
72
K. E. G. K. G. C.
M F F
73 40 61
T. M. B. H. M. H. I. H. L. H.
F F F F M
50 64 57 67 71
M. E.
F
72
A.B. A. P.
M F
36 69
K. L. K. F. E. V.J.
E.V.V 0.N.
F M M F F
16 78 63 57 66
M. P. A. J. I. H. J. A. 0.J. E. L. K. S. K. A. E. J.
F F F M F M F F F
77 61 59 38 69 57 73 40 68
Other diseases, previous or present Liver disease for 10 years Asthma
Duration ofRA (Y.)
Series with gold
Steroid
10
1
10 y ,
21 8 9
2 4 3
34 9 20 6
6 4 1 2 0
1953-58 5 mo. 1964+ 1973 19 y. 9 Y. 0 0 1968-70
23
4
0
20 y.
64
25 7
3 I
0 0
? 1 Y.
24 87
0
9
1 0 1 1 2
0 0 0 0 1964-73
1 0 ? 6 Y. 11 y.
124 40 30 50 80
0
0 2 0 1 7 4 1 9 1
0 0 0 0 11 y. 1956-69 0 5 Y. 0
3 Y.
70 41 38 15 9 34 56 15 30
0
If
Cancer recti; alcoholism Diabetes; heart disease Myxoedema; heart disease
