Risk factors for primary biliary cirrhosis in a cohort of patients from the united states.

Although the etiology of primary biliary cirrhosis (PBC) remains unknown, environmental factors may act to trigger the disease in genetically susceptible hosts. To assess specific risk factors, we conducted a survey using standardized NHANES questions to 241 PBC patients in the United States, 261 of their siblings, and 141 friends without PBC. The overall response rate was 199 of 241 (83%) among PBC cases, 171 of 261 (67%) among siblings, and 141 of 225 (62. 7%) among friend controls. The female-to-male ratio among cases in this sample was approximately 10:1; the mean age was 53 years, and 97% were Caucasian. Other autoimmune diseases reported most frequently by PBC cases included Sjogren's syndrome (17.4%) and Raynaud's syndrome (12.5%). Approximately 6% of cases reported at least one family member with PBC. Adjusted odds ratios (OR) were elevated for cases compared with friends for other autoimmune diseases (OR = 4.92, 95% confidence interval [CI] = 2.38, 10.18), smoking (OR = 2.04, 95% CI = 1.10, 3.78), tonsillectomy (OR = 1.86, 95% CI = 1.02, 3.39), and vaginal or urinary tract infection (UTI) in females only (OR = 2.12, 95% CI = 1.10, 4.07). Similarly elevated ORs were observed for these risk factors when cases were compared with their siblings. The higher rate of UTI among cases is particularly interesting in light of previous data, and raises the possibility of an infectious etiology for PBC and of molecular mimicry as an etiologic mechanism. The significance of smoking in the multivariate models supports the findings of previous studies and raises the issue of the influence of smoking on a Th1 response.

Prevalence of HIV infection, sexually transmitted diseases, and hepatitis and related risk behavior in young women living in low-income neighborhoods of northern California.

OBJECTIVE: To estimate the prevalence of human immunodeficiency virus (HIV) infection, sexually transmitted diseases, and hepatitis and the associated sexual and drug-using behavior among women residing in low-income neighborhoods in 5 northern California counties. METHODS: From April 4, 1996, to January 6, 1998, women aged 18 to 29 years were recruited door-to-door from randomly selected street blocks within 1990 census block groups below the 10th percentile for median household income for each county. RESULTS: Of 24,223 dwellings enumerated, contact was made with residents from 19,546 (80.7%). Within contacted dwellings, 3,560 eligible women were identified and 2,545 enrolled (71.5%). Weighted estimates for disease prevalence were HIV infection, 0.3% (95% confidence interval, 0.1%-0.4%); syphilis, 0.7% (0.3%-1.1%); gonorrhea, 0.8% (0.3%-1.3%); chlamydia, 3.3% (2.4%-4.8%); herpes simplex virus, type 1, 73.7% (71.6%-76.9%); herpes simplex virus, type 2, 34.4% (29.9%-39.0%); hepatitis A, 33.5% (28.3%-38.7%); chronic hepatitis B, 0.8% (0.3%-1.2%); and hepatitis C, 2.5% (1.4%-3. 6%). Condom use at last sexual intercourse with a new partner was reported by 44.0% (33.9%-54.1%). Injection drug use in the last 6 months was reported by 1.8% (1.0%-2.7%). CONCLUSIONS: The Young Women's Survey provided population-based estimates of the prevalence of 8 infectious diseases and related risk behavior within a population for whom data are often difficult to collect. Population-based data are needed for appropriate targeting and planning of primary and secondary disease prevention.

Familial primary biliary cirrhosis in Hiroshima.

Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the presence of anti-mitochondrial antibodies and chronic inflammatory destruction of septal and intrahepatic bile ducts. Although there are no obvious associations of PBC with MHC class I or class II genes, there appears to be a significant increased risk of developing disease within families. Clearly, a combination of genetic and environmental factors play a role in disease pathogenesis, although the relative contributions of each are unclear. In this study, we have taken advantage of the well-defined health-care system in Hiroshima prefecture, where PBC is a reportable disease. In the period 1988-1997, 156 new patients with PBC in a total population of 2,873,000 were diagnosed. These patients included 18 subjects that were derived from eight different families in which more than one family member had a history of PBC; this reflects a frequency of 5.1% and further shows that the prevalence of PBC is greatly increased in family members. Of interest, the median age of onset of PBC in second generation patients was much younger (33.4+/-10.8 years) compared to median disease onset in general patients with PBC in Hiroshima (55.6+/-12 years). In fact, it was striking that the onset of disease in family members often occurred within a few years of each other. We also noted that sera of affected members had similar AMA reactive profiles against recombinant PDC-E2, BCKD-E2 and OGDC-E2; the major autoantigens of PBC. Similar HLA types were found within affected members of a pedigree but the data is limited because of absence of similar typing of unaffected members. The increased family history of PBC, and the earlier onset of disease in second generation members, suggests that environmental agents are an important risk factor for the development of disease. We suggest that genomic analysis in familial PBC will be important to identify the mechanisms of genetic susceptibility.

The geoepidemiology of primary biliary cirrhosis: contrasts and comparisons with the spectrum of autoimmune diseases.

Recent data have suggested that the prevalence of many autoimmune diseases is higher than originally suspected. Indeed, the incidence of some autoimmune diseases may be increasing. Part of the problem in these latter two issues is that there is a dearth of well-designed and controlled epidemiologic studies, and often confounding variables in diverse populations and geographic areas that are not well controlled. Primary biliary cirrhosis (PBC) is a highly directed, organ-specific autoimmune disease that results in the destruction of intrahepatic bile ducts. It is primarily a disease of middle-aged women. Although there is no obvious association with MHC class I or class II alleles, the relative risk of a family member of a first-degree relative within a family having a member with PBC is a hundred-fold that of the general population. Unfortunately, most epidemiologic studies have been descriptive, providing incidence and prevalence rates with many methodologic problems, including lack of an appropriate case definition, varying criteria for inclusion of cases, and inaccurate estimate of the time period to which the rate applies. Because PBC is a very definable disease with significant clinical and serologic overlaps among patients throughout the world, we believe that a review of the geoepidemiology of PBC is not only specifically of value to workers interested in autoimmune liver disease, but also of generic interest in the study of autoimmune disease. In this review, we discuss the nature of the existing epidemiologic data and the possible roles of genetic and environmental factors in the etiology of the disease and compare such data to similar observations for multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis.