Correspondence
Primary Biliary Cirrhosis
N Engl J Med 1997; 336:1387-1388May 8, 1997
- Article
To the Editor:
In his excellent review of primary biliary cirrhosis (Nov. 21 issue),1 Dr. Kaplan states that the serum alkaline phosphatase concentration is “invariably elevated” in this disorder. However, several studies have reported that the alkaline phosphatase concentration may sometimes be normal in the presence of antimitochondrial antibodies and characteristic histologic findings.2,3 My colleagues and I observed “florid duct lesions,” antimitochondrial antibodies, and a normal alkaline phosphatase concentration in the sister of a patient with primary biliary cirrhosis (the biopsy was performed at the time of cholecystectomy).4 Moreover, one recent report has documented the progression over years to more typical primary biliary cirrhosis in such patients, with an associated elevation in alkaline phosphatase.5 This sequence of events has interesting implications in terms of both accurate diagnosis in the early stages of the disease and our understanding of primary biliary cirrhosis. The association between histologic abnormalities and antimitochondrial antibodies at an early stage of the disease supports the possibility that mitochondrial antigens have a role in the pathogenesis of primary biliary cirrhosis.
5 ReferencesStephen H. Caldwell, M.D.
University of Virginia Health Sciences Center, Charlottesville, VA 229081
Kaplan MM . Primary biliary cirrhosis. N Engl J Med 1996;335:1570-1580
Full Text | Web of Science | Medline2
Munoz LE ,Thomas HC ,Scheuer PJ ,Doniach D ,Sherlock S . Is mitochondrial antibody diagnostic of primary biliary cirrhosis? Gut 1981;22:136-140
CrossRef | Web of Science | Medline3
Mitchison HC ,Bassendine MF ,Hendrick A , et al. Positive antimitochondrial antibody but normal alkaline phosphatase: is this primary biliary cirrhosis? Hepatology 1986;6:1279-1284
CrossRef | Web of Science | Medline4
Caldwell SH ,Leung PS ,Spivey JR , et al. Antimitochondrial antibodies in kindreds of patients with primary biliary cirrhosis: antimitochondrial antibodies are unique to clinical disease and are absent in asymptomatic family members. Hepatology 1992;16:899-905
CrossRef | Web of Science | Medline5
Metcalf JV ,James OFW ,Palmer JM , et al. True positive AMA and normal alkaline phosphatase: is this primary biliary cirrhosis? Ten years on, the answer is yes. Gut 1996;38:A634-A634 abstract.
To the Editor:
Kaplan states that patients with primary biliary cirrhosis have striking hypercholesterolemia but are not at increased risk of death from atherosclerosis. This conclusion is based on a study in which 312 patients with primary biliary cirrhosis were observed for a median of 7.4 years and in which the incidence of death from atherosclerosis was not statistically different from that in an age- and sex-matched U.S. control population.1 Most patients in this study were followed as part of a placebo-controlled trial of penicillamine in the treatment of primary biliary cirrhosis. Some patients were treated with lipid-lowering drugs. In 128 patients who died, the causes of death were identified from autopsies in the case of 37 patients, from reports obtained from family members or local physicians in the case of 7 patients, and from death certificates in the remaining 84 patients. The study provided no information on the degree of atherosclerotic disease in surviving patients. We therefore question whether the data are sufficient to justify the above conclusion, which might result in withholding lipid-lowering medication in a patient with primary biliary cirrhosis regardless of the patient's sex, individual lipid levels, or other risk factors.
1 ReferencesU. Leonhardt, M.D.
M. Näther
G. Ramadori, M.D.
Georg-August-Universität, 37075 Göttingen, Germany1
Crippin JS ,Lindor KD ,Joergensen R , et al. Hypercholesterolemia and atherosclerosis in primary biliary cirrhosis: what is the risk? Hepatology 1992;15:858-862
CrossRef | Web of Science | Medline
Author/Editor Response
Dr. Kaplan replies:
To the Editor: Dr. Caldwell is correct. The serum alkaline phosphatase concentration is almost always elevated in primary biliary cirrhosis but not “invariably” so. It has been elevated in over 99 percent of the more than 650 patients whom I have seen with this disease. Atherosclerotic heart disease is uncommon in patients with primary biliary cirrhosis. Levels of high-density lipoprotein cholesterol tend to be disproportionately increased relative to the total cholesterol level,1,2 and Lp(a) lipoprotein levels are low.3 However, atherosclerotic heart disease does occur. A lipid profile should be obtained in patients with elevated serum cholesterol levels. Patients with an increased risk of atherosclerotic heart disease should be treated with diet, appropriate cholesterol-lowering agents, or both.
3 ReferencesMarshall M. Kaplan, M.D.
New England Medical Center, Boston, MA 021111
Jahn CE ,Schaefer EJ ,Taam LA , et al. Lipoprotein abnormalities in primary biliary cirrhosis: association with hepatic lipase inhibition as well as altered cholesterol esterification. Gastroenterology 1985;89:1266-1278
Web of Science | Medline2
Propst A ,Propst T ,Lechleitner M , et al. Hypercholesterolemia in primary biliary cirrhosis is no risk factor for atherosclerosis. Dig Dis Sci 1993;38:379-380
CrossRef | Web of Science | Medline3
Gregory WL ,Game FL ,Farrer M ,Idle JR ,Laker MF ,James OF . Reduced serum lipoprotein(a) levels in patients with primary biliary cirrhosis. Atherosclerosis 1994;105:43-50
CrossRef | Web of Science | Medline
- Citing Articles (2)
Citing Articles
1
Stephen P. James. 2011. Primary Biliary Cirrhosis. , 490-507.
CrossRef2
Carmen M. Stanca, Nancy Bach, Jorge Allina, Carol Bodian, Henry Bodenheimer, Joseph A. Odin. (2008) Atorvastatin Does Not Improve Liver Biochemistries or Mayo Risk Score in Primary Biliary Cirrhosis. Digestive Diseases and Sciences 53:7, 1988-1993
CrossRef
