Journal of Epidemiology Vol. 15, No. 1 January 2005

Transcription

1 Joural of Epidemiology Vol. 15, No. 1 Jauary 2005 Primary biliary cirrhosis (PBC) is a chroic cholestatic disorder characterized by progressive, osuppurative iflammatio ad destructio of small bile ducts, ad the presece of atimitochodrial atibodies (AMA) i the sera. PBC is cosidered to be associated with disturbaces i both cellular ad humoral immuity, but the etiology is still ucertai. Although PBC has bee described i virtually all parts of the world, 1,2 most of the epidemiologic data have bee derived from Europe, 3,4 ad there are ot so may reports from Asia. I Japa symptomatic PBC was specified as oe of "the itractable diseases" from Patiets with symptomatic PBC who wat to receive public fiacial aid from the Miistry of Health, Labour ad Welfare must sig agreemets ad write applicatios. The they are registered ad ca receive the public fiacial aid. The recogitio of patiets with symptomatic PBC is coducted by each prefecture. I 1999, the Miistry of Health, Labour ad Welfare permitted the use of cliical data from the recogized patiets with symptomatic PBC. Most prefectures, but ot all, provided cliical data to the research committee of itractable hepatic diseases. Therefore, the data was also available to the research committee o the epidemiology of itractable diseases. Received August 23, 2004, ad accepted November 2, This study was supported i a part by a grat from the research committee o the epidemiology of itractable diseases of the Miistry of Health, Labour ad Welfare of Japa. 1 Departmet of Public Health, Sapporo Medical Uiversity School of Medicie. 2 Divisio of Gastroeterology ad Hepatology, Departmet of Iteral Medicie, Jikei Uiversity School of Medicie. Address for correspodece: Fumio Sakauchi, Departmet of Public Health, Sapporo Medical Uiversity School of Medicie, South 1, West 16, Chuo-ku, Sapporo , Japa. (sakauchi@sapmed.ac.jp)

2 Sakauchi F, et al. I the preset study, we tried to elucidate the characteristics of patiets with PBC i Japa by utilizatio of the cliical data whe they applied to receive public fiacial aid, ad compared the features of the patiets i Japa with those i other coutries. I the fiscal year 1999, 9,761 prevalet cases with symptomatic PBC were registered. For our cross-sectioal study we used the cliical data of 6,305 patiets because ot all prefectures provided the data, ad chose the cases of 5,805 patiets whose cliical data were writte betwee 1999 ad 2000; the data from residual cases were ot writte durig the time, for example writte i 1998 or before. Patiets whose coditios met oe of the criteria below were diagosed as havig PBC followig the previous reports i Japa Chroic o-suppurative destructive cholagitis (CNC) is histologically observed ad laboratory data do ot cotradict PBC. 2. AMA is positive. CNC is ot histologically observed but histological fidigs are compatible with PBC. 3. Histological examiatio is ot performed, but AMA is positive ad cliical fidigs ad course idicate PBC. For the patiets with symptomatic PBC, the followig iformatio was collected from the records: sex, date of birth, date of diagosis, estimated oset time, symptoms ad physical fidigs, complicated autoimmue diseases, laboratory data icludig serum levels of bilirubi, alkalie phosphatase (ALP), -glutamyl traspeptidase ( -GTP), total cholesterol (T-chole), IgM, ad AMA. We evaluated symptoms ad physical fidigs, laboratory data, ad complicated autoimmue diseases accordig to sex. We also examied the associatio of IgM levels with the positivity of AMA. I the preset study, frequecies of items i the cliical data were aalyzed, excludig "uclear" or blak spaces. Statistical aalysis was performed usig SPSS versio 10.0 (SPSS Ic.). The chi-squared test was used for comparig the proportios of two groups, ad the Ma-Whitey test was used to evaluate differeces i cliical variables. P values less tha 0.05 were cosidered to be statistically sigificat. Table 1. Demographic characteristics of the patiets with primary biliary cirrhosis. No. of patiets 5, ,159 Age (year) stadard deviatio relative frequecy (%) <19 years total Table 2. Symptoms ad physical fidigs of the patiets with primary biliary cirrhosis (%). * Pruritus Jaudice Xathomas Spleomegaly Esophageal varices 53.3 (3,014/5,654) 11.3 (648/5,717) 5.8 (310/5,339) 38.1 (2,/5,508) 19.1 (957/5,012) 57.5 (358/623) 15.4 (97/631) 6.4 (38/595) 37.8 (232/614) 17.3 (95/550) 5 (2,656/5,031) 10.8 (551/5,086) 5.7 (272/4,744) 38.2 (1,868/4,894) 19.3 (862/4,462) p value * : Deomiators are ot equal because frequecies of items were aalyzed, excludig "uclear" or blak spaces. : Chi-squared tests for vs..

3 Primary Biliary Cirrhosis i Japa Table 3. Laboratory fidigs of the patiets with primary biliary cirrhosis. p value ,790 5,021 5,009 4,857 3, ,387 5,655 5,638 5,458 4,450 Total bilirubi (mg/dl) Alkalie phosphatase (ALP: IU/L) -glutamyl traspeptidase ( -GTP: IU/L) Total cholesterol (mg/dl) Immuoglobuli M (IgM: mg/dl) < (4,213/4,895) 90.9 (552/607) 86.6 (4,765/5,502) Atimitochodrial atibody (AMA) positive (%) * : Ma-Whitey tests for vs. : Chi-squared test for vs. : stadard deviatio Age ad sex Table 1 presets the demographic characteristics of the patiets. Of 5,805 patiets, 646 (11%) were, ad 5,159 (89%) were, therefore the male-to-female ratio was approximately 1:8.0, showig a much greater frequecy i. The ad ages of all patiets were 59 ad 60 years, respectively. The age appeared to be somewhat higher i (62 years) tha i (59 years). The highest frequecies were i the 60s for (35.1% for ad 34.0% for, respectively). We tried to estimate the age at the oset of the disease from the records, ad foud that the age was 52 years (55 years for, 52 years for, respectively). Symptoms ad physical fidigs Pruritis was preset i 53.3%, jaudice i 11.3%, xathomas i 5.8%, spleomegaly i 38.1%, ad esophageal varices i 19.1% of all patiets (Table 2). Pruritus ad jaudice were foud sigificatly more frequetly amog tha amog. Laboratory data Key laboratory data are summarized i Table 3. Levels of total bilirubi, ALP, ad -GTP were sigificatly higher amog tha amog, whereas levels of T-Chole ad IgM were sigificatly higher amog tha amog. AMA was positive i 86.6% of all cases, ad its positive rate was sigificatly higher amog tha amog (90.9% for, 86.1% for, respectively). Table 4 shows a sigificat associatio of IgM levels with the positivity of AMA, i.e., a higher IgM level, ad a higher rate of AMA-positive patiets (P for tred ). Complicated autoimmue diseases Complicatios such as Sjögre's sydrome, rheumatoid arthritis, chroic thyroiditis, ad scleroderma icludig CREST sydrome (calciosis, Rayaud's pheomeo, esophageal dysmotility, sclerodactyly, ad telagiectases) were foud i 13.5%, 7.3%, 4.4%, ad 2.0% of patiets, respectively (Table 5). All these complicated diseases were foud sigificatly more frequetly amog tha amog. The patiets with PBC were characterized by a high proportio of, especially of middle age. It has bee reported that 90% to 95% of patiets with PBC are, with a age at the time of diagosis i the early 50s. 8, 9, 10. I Japa, the Research Committee o the Epidemiology of Itractable Diseases coducted two rouds of atiowide surveys of PBC. 11, 12 These surveys reported that the male-to-female ratio was 1: , ad that for the percetage of patiets gradually icreased from their 40s, reachig the highest frequecy age group betwee 60 ad 70

4 Sakauchi F, et al. Table 4. Associatio betwee serum IgM level ad positivity of atimitochodrial atibody (AMA) amog patiets with primary biliary cirrhosis. Immuoglobuli M (IgM: mg/dl) AMA (+) AMA (-) ,430 (82.4) 520 (17.6) Parcetages i paretheses P for tred ,456 (90.2) 158 (9.8) (91.8) 48 (8.2) (96.8) 11 (3.2) Table 5. Parcetages of patiets with primary biliary cirrhosis complicated with selected autoimmue diseases (%). * Sjögre's sydrome Rheumatoid arthritis Chroic thyroiditis Scleroderma 13.5 (683/5,041) 7.3 (390/5,373) 4.4 (258/5,805) 2 (117/5,805) 4.5 (25/555) 2.5 (15/596) 0.8 (5/646) (4/646) 14.7 (658/4,486) 7.9 (375/4,777) 4.9 (253/5,159) 2.2 (113/5,159) p value * : Deomiators are ot equal because frequecies of items were aalyzed, excludig "uclear" or blak spaces. : Chi-squared tests for vs.. years old, while for the former icreased from their 30s ad the latter was betwee 50 ad 60 years old. Regardig the male-to-female ratio ad age distributios of the highest frequecies for, our results approximately agreed with the two reports from the previous atiowide surveys. Ioue et al. also reported that the male-to-female ratio was 1: 7.9, ad the peak icidece was i the 50s. 7 It is still ucertai why are more susceptible to autoimmue diseases, icludig PBC, tha. However, a sex-liked geetic ifluece ad hormoal effect for is oe possible explaatio. 13 Fe are cosidered to have the higher absolute umber of CD4+ lymphocytes tha, ad it is suggested that cytokie secretio is ehaced i the presece of estroge. 14 Moreover, adroges have bee foud to suppress the activity of autoimmue disease such as systemic lupus erythematosus i aimal experimets. 15 Goadal steroids are likely to play importat roles i modulatig autoimmue diseases. Pruritus, jaudice, ad xathomas are usually foud i 55%, 10%, ad less tha 10% of the patiets with PBC, respectively. 1,2 Our results for pruritus, jaudice ad xathomas were similar to our theses values. The percetage of spleomegaly amog patiets with PBC is reported to be 15%, 2 but i the preset study spleomegaly was observed i more patiets tha previously reported. The recet progress of diagostic imagig techiques such as ultrasoography ad computed tomography may be oe possible explaatio for this. Frequecies of jaudice ad biliary ezyme levels were higher amog tha amog. Further studies are required to clarify the associatio betwee sex ad jaudice ad biliary ezymes levels. I Wester coutries it has bee reported that AMA i PBC occurs i 90% to 95% of patiets, 8,16 but the positivity of AMA was lower (86.6% of total patiets). This may be oe of the reasos that Japaese patiets with PBC have lower frequecy of certai types of AMA (e.g. ati-pdc-e2) tha Europeas. 13 More precise laboratory examiatios for various types of AMA might resolve this issue. Lacerda et al. reported that IgM levels were higher i AMApositive tha AMA- egative patiets. 17 Our results also showed a associatio of a higher IgM level with a higher frequecy of AMA-positive patiets. It is reported that Sjögre's sydrome, rheumatoid arthritis, thyroid diseases, ad scleroderma are foud i 75%, 10% to 20%, up to 15%, ad 10% to 15% of patiets with PBC, respectively. 8 Patiets i the preset study had lower frequecies of complicated autoimmue diseases tha those i wester coutries. Other studies i Japa have also reported lower complicatios of these diseases, 5,6,7 but the differece i frequecy of complicated autoimmue diseases betwee Japaese ad Wester people have ot bee clearly explaied. Polymorphism of the huma leukocyte atige (HLA) might be related to the differece i races. 18,19 Our study foud a higher frequecy of complicated autoimmue diseases amog tha amog. This fact also shows that goadal steroids are likely to play importat roles i modulatig autoimmue diseases. I coclusio, usig established recorded data, we described the cliical ad biochemical features of PBC i Japa. The maleto-female ratio, frequecies by age groups, symptoms ad physical fidigs amog patiets with PBC were cosistet with previous reports i Japa ad from other coutries. However, positivity of AMA ad the frequecies of associated autoimmue diseases were lower amog patiets i Japa tha amog those i wester coutries.

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