Liver Disease in Ulcerative Colitis: an Epidemiological and Follow up Study
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84 Gut 1994; 35:84-89 Liver disease in ulcerative colitis: an epidemiological and follow up study in the county of Stockholm Gut: first published as 10.1136/gut.35.1.84 on 1 January 1994. Downloaded from U Broome, H Glaumann, G Hellers, B Nilsson, J Sorstad, R Hultcrantz Abstract sclerosing cholangitis (PSC) are said to be more In an epidemiological study ofthe incidence of common in patients with UC.47 The incidence of ulcerative colitis (UC) in the county of Stock- these complications varies in different studies holm between 1955 and 1979, 1274 patients depending on selection criteria and on the with UC were discovered. Almost all these definition of hepatobiliary disease.89 The true patients had regularly been investigated with incidence of hepatobiliary dysfunction in UC, liver function tests; 142 (11%) of them showed however, can only be obtained by tests of liver signs of hepatobiliary disease. A follow up function tests such as transaminases, alkaline study on all 142 patients with abnormal liver phosphatases, and bilirubin made routinely in function and UC was made between 1989 and unselected groups of patients with UC. Because 1991 to evaluate the cause of the liver abnor- the cause of hepatic involvement in UC is mality and to find out if the liver disease had enigmatic it is important to find out if the rate affected the survival rates. At follow up, eight of this complication is increasing, because of patients were reclassified as having Crohn's factors unrelated to UC, or if it mirrors the disease, 60 had developed normal liver func- incidence ofUC in itself. tion as judged from test results, while the Although it is well established that PSC is a remaining 74 still had signs of hepatobiliary harmful disease often associated with UC'° " the disease. The most common explanation for a importance of pathological liver function tests transient abnormality in liver function was among patients with UC has yet to be estab- active colitis. The temporary signs of liver lished. To find out if hepatobiliary dysfunction injury were not associated with changes in affects the survival of patients suffering from survival rates for these patients. Infections, UC, it is necessary to study the patients for a long especially those because of hepatitis B and period of time. C virus transmitted by blood transfusions In a previously reported epidemiological accounted for the abnormalities in liver func- study,'2 1274 patients with UC were identified in http://gut.bmj.com/ tion in 21 patients, nine ofwhich had a chronic, the county of Stockholm between 1955 and 1979. but non-fatal course. Twenty nine (2.3%) of These patients were subsequently investigated the patients developed primary sclerosing for morbidity and mortality with regard to liver cholangitis (PSC), and 12 of them died during function. In this group, 142 patients were found the study period four because ofcholangiocar- to have abnormal liver function tests and all of cinoma and eight because of hepatic failure; them were studied for an average of 15 years after one patient had a transplant. The estimated the onset ofabnormal liver function tests. on September 25, 2021 by guest. Protected copyright. median time of survival from the first presen- The aims of this study were to establish the tation of evidence of a liver function, com- cause of the liver function abnormalities in all patible with the diagnosis of PSC, to death or 142 patients and to find out whether or not the liver transplantation was 21 years. A compari- liver disease affected the survival of the patients. son of survival rates in patients with UC and patients with UC and concurrent PSC showed, a significant reduction in survival in the PSC Patients and methods Departments of group (p<O-OOOl). The number of patients The basis for this study is an epidemiological Medicine, with UC who developed PSC remained con- investigation of the incidence of UC in Stock- U Broome J Sorstad stant during the study period. Thus, although holm county over a 25 year period. 12 Only R Hultcrantz evidence of abnormal liver function is a com- patients having a definite diagnosis of UC mon finding in UC, a spontaneous return to between 1955 and 1979 and who were residing in Infectious Diseases and Pathology, normal levels is common. In this study, which Stockholm at the time of the diagnosis were H Glaumann did not have a selection bias, the median time included. A total of 1274 patients, 681 males and of survival among PSC patients was far longer 593 females, with UC were found.'3 Twenty five Surgery, than previously described although develop- per cent of the patients suffered from proctitis, G Hellers ment of PSC among patients with UC does defined as mucosal changes found at proctosig- Oncology, significantly reduce the estimated median time moidoscopy, with a clear definition between the B Nilsson of survival. affected rectal mucosa and the normal mucosa in Karolinska Institute at (Gut 1994; 35: 84-89) more proximal parts of the colon and a barium Huddinge, St Goran and enema without further pathology. Thirty eight Karolinska Hospitals, per cent presented with mucosal changes in the Stockholm, Sweden The association of ulcerative colitis (UC) and rectum and radiological changes in the distal Correspondence to: Dr U Broome, Huddinge liver disease was first described in 1873 and was colon (reaching in proximal direction no further Hospital, Department of followed by numerous surveys of liver dysfunc- than to the hepatic flexure) and were defined as Medicine K63, 141 86 Huddinge, Sweden. tion in UC. 1-3 A number of liver disorders, such having left sided colitis. Thirty seven per cent of Accepted for publication as fatty change, chronic autoimmune hepatitis, the patients had total colitis, defined as mucosal 26 May 1993 liver cirrhosis, cholangiocarcinoma, and primary changes in the rectum and radiological evidence Liverdisease in ulcerative colitis: an epidemiological andfollow up study in the county ofStockholm 85 of disease in the colon beyond the hepatic smooth muscle, raised IgG, and negative tests for flexure. All but 55 patients were regularly hepatitis B was required.'5 investigated with liver function tests. Patients Positive markers for hepatitis B (presence of with evidence ofabnormal liver function tests (at surface antigen and antibodies to core antigen) or Gut: first published as 10.1136/gut.35.1.84 on 1 January 1994. Downloaded from least twice the upper normal values of serum antibodies to hepatitis C, proved with the recom- bilirubin, serum activities of alkaline phos- binant immunoblot analysis (RIBA C100-3, phates, or liver transaminases, or all three at two Chiron) and a liver biopsy compatible with occasions with a minimal interval oftwo months) chronic viral hepatitis were interpreted as indica- were defined as having hepatobiliary disease. tive of chronic hepatitis B or C infection. Onset of liver disease was defined as the time of The patients were diagnosed as having a liver the first abnormal liver function tests. One abnormality as a result ofactive colitis ifevidence hundred and forty two patients, 92 males and 50 of abnormal liver function tests was found only females, with UC and abnormal liver function during periods of inflammatory activity in the tests were identified. bowel, as defined by diarrhoea and sigmoido- scopic findings of excess mucus, signs of bleed- ing, or ulcerations, or all three and if the liver METHODS function tests returned to normal after colectomy The files from all 142 patients, both living and or when the patients were in remission and no deceased (n=35), with UC and signs of hepato- other explanation for the abnormality in liver biliary disease were re-evaluated during the years function tests was found. Fatty change was 1989 and 1991. Ifno current data were available, believed to be the cause of increased activities of patients were asked to have liver function tests. transaminases if the patients showed an isolated If no clinical signs of liver disease were present increase in these enzymes unrelated to inflamma- and aspartate aminotransferase and alanine tory activity in the bowel, were overweight aminotransferase were <1-0 iikat/l and alkaline (calculated from as weight (kg)/length (cm)- phosphatase <5 0 pkat/l no further investiga- 100>1), and with no other explanation for tion was carried out. Attempts were made to abnormal liver function tests, such as alcohol retrospectively clarify the cause of the previous abuse. 6 abnormalities in liver function tests. All slides from biopsy specimens and liver All patients with a persistent rise in alkaline tissue obtained at necropsy were re-evaluated by phosphatase >5 [ikat/l (normal upper range one liver pathologist (HG) and one hepatologist <4-2 ,ukat/l) had an ultrasound investigation (UB) according to the international classification and subsequently also an endoscopic retrograde of liver diseases and without knowledge of the cholangiography or percutaneous transhepatic clinical data concerning the patients.'7 cholangiography. http://gut.bmj.com/ All patients with a persistent rise in trans- aminase activities and without a previously STATISTICAL ANALYSES established hepatobiliary diagnosis were Student's t test was used to compare mean examined with conventional laboratory tests and values, and X2 analysis to compare proportions. were questioned concerning intake of alcohol or Survival curves were estimated by the method of drugs, and exposure to other hepatotoxic sub- Kaplan and Meyer and differences between stances. Laboratory tests included assessment of groups were compared using the log rank test. As on September 25, 2021 by guest. Protected copyright. serum y-glutamyltransferase, bilirubin, creati- the development of PSC can be considered to be nine and ferritin, and serum protein electro- time dependent after the development of UC, an phoresis regarding values of ceruloplasmin and analysis of survival curves for patients with both al anti-trypsin.