Primary biliary cirrhosis: survival of a cohort followed for 10 years.

OBJECTIVES: To study the natural course of primary biliary cirrhosis (PBC) in order to be able to design accurate clinical pharmacological studies and evaluate the need for liver transplantation. DESIGN: A cohort of 86 patients with PBC living in northern Sweden was followed for a 10-year period during 1983-93. No patients received therapy with ursodeoxy cholic acid or other drugs during the follow-up period. METHOD: At start all patients were investigated personally by the authors. At follow-up medical notes were scrutinized and special questionnaires to the current responsible physician were applied. Endpoints were the time of dropout, liver transplantation, death or end of the study period. RESULTS: At follow-up data were available for 84 patients (97%). During the study period 34 patients died, of whom 28 were symptomatic; 15 deaths had no direct connection to PBC. Nineteen deaths were related to PBC of whom two were asymptomatic, the most common cause being end-stage liver disease with liver coma. During the study period in all eight patients were subjected to liver transplantation. CONCLUSIONS: The survival rate of the 32 asymptomatic PBC patients at the start of the study was the same as a sex- and age-matched standard background population. Those patients with symptomatic PBC from the beginning of study had a survival rate at 10 years of 50%, and the most ominous sign was a bilirubin greater than 35 micromol L(-1) . Liver transplantation was performed in almost 10% in this cohort until 1993. Since then, the indications and referral practice for liver transplantation has changed and is now higher.

Importance of synovial fluid aspiration when injecting intra-articular corticosteroids.

OBJECTIVE: The aim of this prospective study was to find if a complete synovial fluid aspiration before injecting intra-articular corticosteroids influences the treatment result. METHODS: The study was performed in 147 patients with rheumatoid arthritis (RA). One hundred and ninety one knees with synovitis were randomised to arthrocentesis (n=95) or no arthrocentesis (n = 96) before 20 mg triamcinolone hexacetonide was injected. The duration of effect was followed up for a period of six months. All patients were instructed to contact the rheumatology department if signs and symptoms from the treated knee recurred. If arthritis could be confirmed by a clinical examination a relapse was noted. RESULTS: There was a significant reduction of relapse in the arthrocentesis group (p = 0.001). CONCLUSION: The study shows that aspiration of synovial fluid can reduce the risk for arthritis relapse when treating RA patients with intra-articular corticosteroids. It is concluded that arthrocentesis shall be included in the intra-articular corticosteroid injection procedure.

A double-blind comparison of oral ketoprofen 'controlled release' and indomethacin suppository in the treatment of rheumatoid arthritis with special regard to morning stiffness and pain on awakening.

A double-blind, double-dummy, crossover study was carried out in 8 centres to compare the efficacy and tolerability of 'controlled-release' ketoprofen tablets (200 mg) with that of indomethacin suppositories (100 mg) in out-patients with definite or classical rheumatoid arthritis. Patients were allocated at random to receive a daily bedtime dose of either 1 ketoprofen tablet or 1 indomethacin suppository plus the dummy of the other formulation for a period of 3 weeks. They were then crossed over to the alternative treatment for a further 3 weeks. Daily diary records were kept by patients of the number of night-time awakenings due to pain, pain severity at awakening in the morning and the duration of early morning stiffness. Treatment efficacy was also assessed at the end of each trial period by means of an articular index and by physician's and patient's overall evaluation of response. Adverse effects spontaneously mentioned by the patients or elicited by direct questioning using a symptom check-list were recorded. Statistical analysis of the results from 83 evaluable patients showed that the 'controlled-release' tablet formulation of 200 mg ketoprofen was equally as effective as the 100 mg indomethacin suppository in the treatment of rheumatoid arthritis, especially with regard to pain at awakening and morning stiffness. Side-effects in both groups were those commonly seen with non-steroidal anti-inflammatory drugs and, as expected, gastro-intestinal and CNS disturbances predominated. Overall, side-effects were fewer with ketoprofen than with indomethacin.

Features of Sjögren's syndrome in patients with primary biliary cirrhosis.

Twenty-six consecutive patients with primary biliary cirrhosis (PBC) from northern Sweden were studied regarding the occurrence and features of Sjögren's syndrome (SS). In more than 50% of the patients the rose bengal dye test showed conjunctival and/or corneal staining. In six patients keratoconjunctivitis sicca (KCS) was present with positive rose bengal and Schirmer tests. In a further three patients only the results of the Schirmer tests were abnormal. Radiological findings of sialectasia were demonstrated in six patients, five of whom had KCS. Two of the seven patients who fulfilled our criteria for Sjögren's syndrome were HLA-B8 positive. A high prevalence of increased immune globulins and rheumatic factor was found, but this did not correlate with the presence of Sjögren's syndrome. Some features of Sjögren's syndrome were found in 73% of PBC patients, and keratoconjunctivitis sicca and/or sialectasia were found in 27% of PBC patients. This constitutes a high frequency of secondary manifestations of the liver disease.

Epidemiology of primary biliary cirrhosis in a defined rural population in the northern part of Sweden.

The northern part of Sweden is sparsely populated and must be regarded as a rural region. An investigation into the incidence and prevalence of primary biliary cirrhosis was conducted and the course of the disease was followed. In total, 111 patients with primary biliary cirrhosis were identified for the 10-yr period 1973 to 1982 in the northern health region of Sweden. The mean annual incidence amounted to 13.3 per million and the point prevalence was 151 per million, which is the highest reported so far. There was a significantly higher prevalence in the most northern county of Sweden, both with respect to total number of primary biliary cirrhosis patients and symptomatic patients. Asymptomatic patients amounted to 37%. During the study period 25 patients out of the 111 died (23%), 14 as a direct consequence of the liver disease. Three patients died of primary hepatocellular carcinoma, one having an asymptomatic liver disease without cirrhosis. Primary biliary cirrhosis seems to be more common in Sweden, especially in the northern part, than it is elsewhere. A high frequency of extrahepatic symptoms (85%), mainly musculoskeletal, was recorded. These symptoms may lead to the first contact with the health service, rather than signs of liver disease. Thus, an increasing number of patients are diagnosed with asymptomatic liver disease, who must be followed to check for the eventual development of symptoms.

Alterations in C1 inhibitor and clotting factor concentrations in primary biliary cirrhosis and other chronic liver diseases.

C1 inhibitor and von Willebrand factor (vWF) levels were studied in patients with cholestatic or hepatocellular liver diseases. The vWF levels were greatly increased in hepatocellular liver diseases, whereas C1 inhibitor levels were slightly reduced. In cholestatic disease both the vWF and the C1 inhibitor levels were increased: among patients with primary biliary cirrhosis these increases were more pronounced in symptomatic patients than in asymptomatic ones. When compared with other protease inhibitors, the C1 inhibitor pattern in liver disease most closely resembled that of alpha 1-antitrypsin. Thus, C1 inhibitor levels cannot be used as a measure of residual hepatocyte mass in PBC; our data, however, suggested that antithrombin may be more suitable for that purpose.

Lung function abnormalities in patients with primary biliary cirrhosis.

Twenty-five patients with primary biliary cirrhosis (PBC) in different stages were investigated with respect to pulmonary function abnormalities. The results were compared with a reference sample of 17 sex- and age-matched healthy subjects. A high prevalence of lung function impairment was found in the PBC patients (14/25 [56%]). Bronchial asthma was present in three patients, and severe lung emphysema in one. These four patients had an abnormal lung function, mainly of obstructive type. There was a statistically significant difference between the remaining 21 PBC patients without chronic obstructive lung disease and the reference subjects with respect to diffusion capacity. Almost all abnormal lung function data were found in the symptomatic PBC patients (i.e. symptoms of pruritus, xanthoma, xanthelasmata, jaundice, hyperpigmentation, hepatosplenomegaly), 13 out of 18 (72%), whereas only one out of seven asymptomatic patients was affected. Nine patients (36%) had reduced diffusion capacity compared with none of the reference subjects. The lung function abnormalities in PBC patients are similar to those found in sarcoidosis, another granulomatous disease.

Evaluation of rheumatic disorders in patients with primary biliary cirrhosis.

Twenty-six consecutive patients with primary biliary cirrhosis (PBC) were subjected to clinical, radiological and serological assessment for evidence of rheumatic disease. Seven patients had asymptomatic liver disease, while the rest had symptoms indicating varying stages of advanced disease. Of the 18 patients with arthropathy, in 13 there was considered to be an association between the arthropathy and PBC as no other underlying causes could be discovered. In about half of the patients the symptoms were episodic, while the others had chronic pain. Usually both large and small joints were affected bilaterally. The joint symptoms had an average duration of 5 years, and had started in all patients after the onset of the liver disease. All 7 patients with arthritis fulfilled the criteria of the American Rheumatism Association for rheumatoid arthritis (RA). Five patients were classified as definite or classical RA. Circulating immune complexes were present in 35% of all patients, but there was no correlation with the presence of arthropathy. Seven patients were HLA-B27 positive, of whom 4 had arthritis. The investigation demonstrates that rheumatic disorders are common in PBC patients, whether or not they are symptomatic, and sometimes joint symptoms may even dominate the clinical picture.

Kveim test and mitochondrial antibodies in the differential diagnosis between primary biliary cirrhosis and sarcoidosis.

Intracutaneous Kveim test and measurement of serum mitochondrial antibodies were performed in a group of patients with primary biliary cirrhosis (PBC) and in a group of patients with sarcoidosis. There were 14 patients, 1 man and 13 women, age range 39-64 years, with clinical picture, laboratory tests and liver biopsy consistent with PBC. In the sarcoidosis group there were 38 patients, 18 men and 20 women, age range 22-76 years, with clinical, radiological and histopathological findings typical for sarcoidosis. In this group chest x-ray showed stage 0 in 3 patients, stage I in 7, stage II in 18 and 10 patients were in stage III. Kveim test was positive in 24 (63.2%) of the sarcoid patients and negative in all 14 patients with PBC. Mitochondrial antibodies were present in 13 of the PBC-patients but in none of the 38 examined sarcoid patients. Kveim test and analysis of mitochondrial antibodies seems to be of great value in the differential diagnosis between primary biliary cirrhosis and sarcoidosis.

Musculo-skeletal symptoms in early sarcoidosis. Twenty-four newly diagnosed patients and a two-year follow-up.

Musculo-skeletal symptoms were screened in 24 consecutive patients with newly diagnosed sarcoidosis and followed up two years later. Ten patients had joint involvement. Symptoms were most frequently found in ankle joints, followed by hand and knee joints. Arthritis was found in seven (29%) patients, two of whom suffered from monoarthritis of foot and wrist joint, respectively. Three patients had tenosynovitis. Muscle symptoms such as myalgia were present in six patients. Open biopsy of the gastrocnemius muscle showed epithelioid cell granulomatosis in nine of 20 patients. Only three of these nine patients had symptoms of myalgia, although not in the biopsied muscle. At follow-up, musculo-skeletal symptoms were found in only three patients, all of whom initially had Löfgren's syndrome.

Muscle involvement in sarcoidosis.

In 22 patients with sarcoidosis, symptoms and signs of muscle involvement were scanty, but muscle biopsy showed epithelioid cell granulomas consistent with sarcoidosis in 11 patients (50%). Serial sectioning of the muscle biopsies increased the diagnostic yield. The incidence of muscle involvement was highest among patients with both acute sarcoidosis and erythema nodosum. Involvement of other organs was common in patients with muscle sarcoidosis. In two patients with negative scalene node biopsy and negative bronchial and transbronchial biopsies, muscle biopsy showed histological evidence of sarcoidosis. Muscle involvement is common in patients with sarcoidosis, but in many cases there are few or no symptoms. In patients with both acute sarcoidosis and erythema nodosum, muscle biopsy frequently provides histological evidence of the disease. Good cooperation with the pathologist and serial sectioning of the biopsies are necessary if muscle biopsy is to be used as a routine in the diagnosis of sarcoidosis.