Biomedical subjects

D E Jones

Publications and source records attributed to D E Jones.

At least 37 records · Page 2Linked to original sources

PubMed2000

Presentation and mortality of primary biliary cirrhosis in older patients.

OBJECTIVES: many patients with primary biliary cirrhosis present for the first time aged over 65, but it is unclear whether the disease is different in older patients. We have examined presentation and mortality in relation to age at which primary biliary cirrhosis was first suspected clinically. DESIGN: we identified 1023 patients from our regional primary biliary cirrhosis database with definite or probable primary biliary cirrhosis (689 definite); 397 (39%) presented aged > or =65. Definite primary biliary cirrhosis was defined as a positive antimitochondrial antibody titre > or =1/40, abnormal liver enzymes and compatible/diagnostic histology; probable as the presence of two of these indications. RESULTS: there was no difference in presenting clinical features between the older and younger groups. Older patients were significantly less likely than younger to have had liver biopsy (50% vs 78%; P < 0.001). The 1023 patients had been followed for 8561 patient years. Follow-up was shorter (5.9+/-4 vs 9.8+/-5.5 years; P < 0.001) in the older group because of higher cumulative mortality (59% vs 33%; P < 0.001). Liver-related deaths were significantly commoner in the older group (18% vs 13%; P < 0.05). The mortality ratio for liver deaths (liver deaths per year of follow-up) was 2.4 times higher in the older group (0.031 vs 0.013). CONCLUSIONS: patients with primary biliary cirrhosis who are over and under 65 have similar features on presentation. The annual risk of liver death is 2.4 times higher in those presenting over 65, reaffirming the importance of age as an independent prognostic factor in an unselected primary biliary cirrhosis population.

Adult↗

PubMed2000

Autoantigens in primary biliary cirrhosis.

The automimmune liver disease primary biliary cirrhosis (PBC) is characterised by serum autoantibodies directed at mitochondrial and nuclear antigens (seen in most patients and a subset of patients, respectively). The antimitochondrial antibodies (AMA) characteristic of PBC are directed at members of the 2-oxoacid dehydrogenase components of multienzyme complexes; in particular, the E2 and E3 binding protein (E3BP) components of the pyruvate dehydrogenase complex (PDC). The presence of autoantibodies reactive with PDC-E2 and/or E3BP is strongly predictive of the presence of PBC. Therefore, the detection of these antibodies plays a very important role in the diagnosis of PBC. Originally demonstrated using immunofluorescence approaches, AMA can now be detected by the use of commercially available enzyme linked immunosorbent assays (ELISAs). Although the ELISA based approaches have advantages in terms of laboratory practicality, they are slightly less sensitive for the diagnosis of PBC than immunofluorescence (occasional patients with PBC show reactivity with PDC related antigens not present in the antigen preparations available for use with ELISA). Therefore, immunofluorescence should continue to be available as a complementary diagnostic test for use in occasional patients. In a subset of patients with PBC, autoantibodies are directed at increasingly well characterised nuclear antigens. Antinuclear antibody (ANA) positive patients are typically AMA negative. There are no significant differences in disease phenotype between AMA positive and AMA negative groups. At present, the clinical detection of ANA is mostly by Hep2 immunofluorescence, although ELISA kits for individual nuclear antigens are increasingly becoming available.

Antigens, Nuclear↗

PubMed2000

Primary biliary cirrhosis: new perspectives in diagnosis and treatment.

Primary biliary cirrhosis (PBC) is a chronic autoimmune disease characterised by cholestatic liver function tests, antimitochondrial antibodies, and abnormal liver histology. Early descriptions of a rare rapidly progressive disease no longer reflect the more indolent progress often seen today. Many patients have significant long term morbidity through symptoms such as fatigue and itch with a minority progressing to liver failure and need for transplantation. The current data on the diagnosis, clinical progression, and treatment of PBC are reviewed.

Humans↗

PubMed2000

Multi-step polymer-assisted solution-phase (PASP) library synthesis of functionalized diaminobenzamides.

A parallel solution-phase library synthesis of functionalized diaminobenzamides is described. The four-step library synthesis is accomplished using polymer-assisted solution-phase (PASP) synthesis techniques. This high-yielding, multi-step sequence utilizes sequestering resins for the removal of reactants, reactant by-products, and employs a resin capture/release strategy as a key library synthesis step. Step one of the sequence relies on the displacement of an activated fluoro-group from the aromatic ring of 1a, b with a variety of primary amines to introduce the first diversity position. Step two is hydrolysis of the benzoate ester to a benzoic acid which is subsequently captured on a polyamine resin, washed, and released to give 4a, b in pure form. Step three utilizes PASP resins to mediate the amide coupling of a benzoic acid with a variety of primary amines to give the aminonitrobenzamides 5a, b and introduces the second diversity position. Step four is the parallel reduction of the aminonitrobenzamides 5a, b to the functionalized diaminobenzamides 6a, b. This library synthesis proceeds with high overall purities which average 80 % over the 4-step sequence.

Amines↗

PubMed2000

Neurodevelopmental effects: making the case for biologic plausibility.

It has been suggested that the most critical missing link between science and policy is causality; that is, the establishment of a definite cause-effect relationship between exposure and adverse health effects. As has been clearly demonstrated by the decades-long tobacco debate, causality is extremely difficult to establish with absolute certainty, particularly in the minds of scientists. Because of this, it has been suggested that a "weight of evidence" approach based on biologic plausibility should be used as a surrogate for causality when translating science into policy and public health practice. In the case of neurodevelopmental effects, the case for biologic plausibility is supported by scientific findings from three broad areas consisting of wildlife biology, toxicology, and epidemiology. A striking example of this is provided by research findings from the Great Lakes Basin, an area which has been the focus of significant scientific research for the last thirty years in these three broad areas. In this paper, we examine relevant findings from the Great Lakes Basin and elsewhere as they relate to establishing and supporting the biologic plausibility of neurodevelopmental effects associated with environmental exposures to persistent toxic substances.

Animals↗

PubMed1999

The integral divalent cation within the intermolecular purine*purine. pyrimidine structure: a variable determinant of the potential for and characteristics of the triple helical association.

In vitro assembly of an intermolecular purine*purine.pyrimidine triple helix requires the presence of a divalent cation. The relationships between cation coordination and triplex assembly were investigated, and we have obtained new evidence for at least three functionally distinct potential modes of divalent cation coordination. (i) The positive influence of the divalent cation on the affinity of the third strand for its specific target correlates with affinity of the cation for coordination to phosphate. (ii) Once assembled, the integrity of the triple helical structure remains dependent upon its divalent cation component. A mode of heterocyclic coordination/chelation is favorable to triplex formation by decreasing the relative tendency for efflux of integral cations from within the triple helical structure. (iii) There is also a detrimental mode of base coordination through which a divalent cation may actively antagonize triplex assembly, even in the presence of other supportive divalent cations. These results demonstrate the considerable impact of the cationic component, and suggest ways in which the triple helical association might be positively or negatively modulated.

Base Pairing↗

PubMed1999

Development of autoimmune hepatitis following liver transplantation for primary biliary cirrhosis.

Two patients undergoing liver transplantation for classical end-stage primary biliary cirrhosis (PBC) are described, who went on to develop de novo autoimmune hepatitis (AIH) in the transplanted liver. The presentation, in both instances, was with malaise and lethargy. Markedly elevated serum transaminases were found, together with a raised serum IgG and/or globulin fraction and histological features on liver biopsy typical of AIH. Both cases had had changes in their immunosuppressive therapy before the onset of AIH episodes, and both rapidly responded to reinstitution of steroid therapy. The finding, in each case, of a coincidental multiple HLA class I allele match between the recipient and their liver donor suggests that HLA class I-restricted mechanisms may play an important role in the pathogenesis of AIH.

Female↗

PubMed1999

Characterization of the autoantibody responses to recombinant E3 binding protein (protein X) of pyruvate dehydrogenase in primary biliary cirrhosis.

Autoantibodies to the pyruvate dehydrogenase complex (PDC) are present in the serum of more than 95% of patients with primary biliary cirrhosis (PBC), the major epitope being the inner lipoyl domain of the E2 component. Immunoblotting suggests a similar prevalence of antibodies to a tightly associated lipoic acid-containing protein, E3 binding protein (E3BP). Attempts to resolve E3BP from E2 have been unsuccessful, restricting study of the nature and significance of antibody responses to the individual proteins. In particular, it is unclear (1) whether there is true cross-reactivity between E3BP and E2 and, if so, which is the originating response and (2) whether autoantibodies preferentially bind a lipoylated epitope on E3BP as is the case with PDC-E2. In this study, complementary DNAs encoding rE2, full-length rE3BP, its single lipoyl domain (rLip), and core domain (rE3BPCore) were cloned, and the proteins were expressed in Escherichia coli. Sera from 47 PBC patients were studied by immunoblotting and enzyme-linked immunosorbent assay (ELISA) against rE2, rE3BP, rE3BPCore, and both unlipoylated (U) and lipoylated (L) rLip. All sera were reactive by ELISA to some degree with all recombinant proteins except rE3BPCore, to which only 6 of 47 showed any reactivity. Significant correlations (P <.0001) were observed when comparing absorbance values for rE3BP with both rLip (U) (r = 0.793) and (L) (r = 0.963). The mean absorbance for rLip (U, 0.26 +/- 0.05) was, however, significantly lower than the absorbance for rLip (L) (0.78 +/- 0.12; P <.0001). After probing by immunoblotting and elution of antibodies from rE2 and rE3BP, subsequent reprobing against the components in whole PDC revealed true cross-reactivity. In summary, the response to E3BP is primarily directed against the lipoylated domain of the protein. It still remains unclear, however, whether the initial breakdown of tolerance is to E2 or E3BP.

Antibody Formation↗

PubMed1999

Breakdown of tolerance to pyruvate dehydrogenase complex in experimental autoimmune cholangitis: a mouse model of primary biliary cirrhosis.

The autoimmune liver disease primary biliary cirrhosis (PBC) is characterized by autoreactive responses to a highly conserved self-antigen, pyruvate dehydrogenase complex (PDC). We recently reported the development of PBC-like lesions in SJL mice sensitized with PDC and have named this model disease experimental autoimmune cholangitis (EAC). In the present study, the breakdown of tolerance to PDC has been investigated in animals sensitized for EAC. Splenic mononuclear cells from SJL mice sensitized with bovine heart PDC (bPDC) in adjuvant showed T-cell proliferative and mixed Th1/Th2 cytokine secretory responses following in vitro stimulation with bPDC. Despite the likelihood of extensive sequence homology with mouse PDC (there is a greater than 95% sequence identity between rat and human PDC-E2 subunits), bPDC was highly immunogenic inducing significant T- and B-cell responses in the absence of any form of adjuvant. The multi-subunit quaternary structure of intact PDC was critical for this immunostimulatory activity because no response was produced by sensitization with monomeric recombinant PDC-E2 inner lipoyl domain. Mice sensitized with bPDC and CFA developed, within 2 weeks of sensitization, high-titer antibody responses reactive with bPDC that were fully cross-reactive with the murine homologue. Breakdown of T-cell tolerance to self-PDC took significantly longer, not being seen until 20 weeks postsensitization; a similar length of time to that previously shown to be required for EAC lesion development. Conclusions drawn from these data may have important implications for our understanding, and therapeutic manipulation, of PBC in humans.

Animals↗

PubMed1999

Supracervical hysterectomy: back to the future?

Supracervical hysterectomy, commonly performed in the earlier decades of this century, is rarely performed in contemporary practice. The desire to prevent future cervical cancer initially underlay the advocacy of total hysterectomy. Cervical cytologic screening and effective outpatient treatment of preinvasive cervical disease are commonly available. Cancer of the cervical stump is an uncommon and largely preventable occurrence. Removal of the normal cervix reportedly may have adverse effects on bladder, bowel, and sexual function. Reduced operating time and a shorter recovery period may be associated with a supracervical procedure. The risk of subsequent cervical cancer may not outweigh the benefits of supracervical hysterectomy, which should be offered as an option to selected patients. Supracervical hysterectomy by minilaparotomy is within the capability of practicing gynecologists and may be adaptable to outpatient short-stay surgery, offering a cost-effective alternative for a variety of gynecologic conditions.

Ambulatory Surgical Procedures↗

PubMed1999

Influence of specialty on pathology resource use in evaluation of cervical dysplasia.

OBJECTIVE: Colposcopy is performed by different providers, including nurse practitioners, family physicians, and gynecologists. The training and experience of these providers vary. The fiscal impact of provider type is unknown. This study evaluates pathology resource use by gynecologists and nongynecologists at the time of colposcopy. METHODS: A retrospective cohort study was performed. Data were collected by review of pathology reports and records of all patients with cervical dysplasia treated with cervical excision by loop electrosurgical excision procedure or cold knife conization at our institution between January 1, 1996, and December 31, 1997. Data were analyzed according to type of provider performing the colposcopy before the cervical excision. RESULTS: Gynecologists obtained a total of 190 biopsy specimens in 127 patients, with a mean number of 1.5 +/- 0.75 per patient and a median of 1. Nongynecologists took a total of 148 biopsy specimens in 44 patients, with a mean of 3.4 +/- 1.14 per patient and a median of 3 (P < .001). These differences persisted irrespective of presenting cytology. Nongynecologists were more likely to do endocervical curettage than gynecologists (95% compared with 82%, respectively, P < .001). Cervical dysplasia was diagnosed equally well, even though fewer biopsies were taken by gynecologists. CONCLUSION: Both groups of providers were equally capable of identifying dysplastic lesions. Despite equivalent diagnostic accuracy, nongynecologists used two to three times more pathology resources. If this pattern of use of resources exists at other clinical sites, patients with cervical dysplasia and payers would be better served by gynecologic rather than nongynecologic care.

Adult↗

PubMed1999

Tumour necrosis factor-alpha promoter polymorphisms in primary biliary cirrhosis.

BACKGROUND/AIMS: The incidence of primary biliary cirrhosis (PBC) is increased in the close relatives of patients, suggesting that genetic factors play a role in disease susceptibility. Decreased in vitro production of tumour necrosis factor (TNF)-alpha has been reported in PBC patients, suggesting a potential aetiological role for this cytokine. The aim of this study was to examine two biallelic polymorphisms in the promoter region of the TNF-alpha gene, which may play a role in the control of TNF-alpha secretion, as candidate susceptibility loci in PBC. METHODS: The polymorphisms at positions -238 and -308 in the TNF-alpha promoter region were analysed by polymerase chain reaction in 168 unrelated PBC patients and 145 local unrelated, geographically matched normal individuals. All PBC subjects were also genotyped for HLA DR8, a previously identified susceptibility locus in PBC. RESULTS: The -308 TNF1/TNF1 genotype was seen in a similar proportion of PBC patients (66%) and controls (60%). However, this genotype was found significantly more frequently in the 95 PBC patients with more advanced disease (histological stage III/IV) (77%) than in either controls (p<0.01, OR = 2.2 [1.2-4.0]) or the PBC patients with earlier disease (38/73 (52%), p = 0.001 OR 3.1 [1.6-5.9]). Linkage between TNF -308 and HLA DR8 was not seen. No association was found between PBC and the biallelic -238 TNF-alpha polymorphism, either in the whole PBC population or the histological Stage III/IV subgroup. CONCLUSIONS: Our study provides no evidence for involvement of the TNF-alpha -308 or -238 promoter polymorphisms in genetic predisposition to PBC. However, the significantly increased frequency of the -308 TNF1/TNF1 genotype seen in 95 patients with more advanced disease raises the possibility that this allele may be linked to disease progression rather than susceptibility. The finding of different allele frequencies in PBC patients in different disease subgroups emphasises the importance of clinical phenotype/casemix in the design of disease association studies.

Aged↗

PubMed1999

Familial primary biliary cirrhosis reassessed: a geographically-based population study.

BACKGROUND/AIMS: Development of primary biliary cirrhosis in the close relatives of patients with the disease has been reported in several series, suggesting a genetic component to disease susceptibility. In this study we set out to calculate, as accurately as possible, the prevalence of familial primary biliary cirrhosis in a geographically-based population. Using local population prevalence data, we have also calculated the first-degree relative, sibling and offspring relative risks of overt primary biliary cirrhosis development. METHODS: All patients with definite or probable primary biliary cirrhosis in the city of Newcastle-upon-Tyne, England, were identified by an exhaustive case-finding search and were prospectively interviewed by a single investigator. Full details of family pedigree and familial primary biliary cirrhosis history were obtained. RESULTS: One hundred and seventy-three patients were identified, with 160 participating in the study. Thirteen reported a family history of primary biliary cirrhosis. In three cases, both relative pairs were within the study group. The prevalence of a positive family history of primary biliary cirrhosis was therefore 10/157 (6.4% [95% Confidence Interval 2.6-10.2%]), 8/10 cases occurring in first-degree relatives. The patients had a total of 1118 first-degree relatives (live or dead) and 468 siblings. The first-degree relative prevalence of primary biliary cirrhosis was 0.72% [0.2-1.2%] (siblings 0.41% [-0.2-1.0%]). The offspring prevalence was 1.2% [0.04-2.4%], (2.3% [0.1-4.5%] for daughters). The sibling relative risk (lambda(s)) was 10.5. CONCLUSIONS: The overall prevalence of definite or probable primary biliary cirrhosis in the first-degree relatives of existing patients is <1%. The risk of disease is not, however, uniform, the highest prevalence being seen in the daughters of patients. Suspicion of disease should therefore be highest in this relative group. The calculated lambda(s) for primary biliary cirrhosis in this geographically-based study is significantly lower than previous estimates from case-note-derived case series, but similar to values seen in other autoimmune diseases.

Adult↗

PubMed1999

T cell responses to the putative dominant autoepitope in primary biliary cirrhosis (PBC).

PBC is characterized by T cell-mediated destruction of the biliary epithelial cells lining the small intrahepatic bile ducts. The E2 and E3 binding protein (E3BP (protein X)) components of pyruvate dehydrogenase complex (PDC) are disease-specific autoantigens in PBC. Attempts to localize the T cell autoepitopes within PDC-E2 have, however, generated contradictory results. One study has suggested the presence of T cell epitopes throughout PDC-E2, whilst another has identified a single dominant 14 amino acid T cell epitope (p163) spanning the lipoic acid binding lysine residue in the inner lipoyl domain (ILD) of PDC-E2. The aim of the current study was to determine the prevalence of T cell responses to p163 and PDC-E2 ILD, and the role played by lipoylation of these antigens in their immunogenicity, in a UK PBC population. We found that the majority of the PBC patients showing a 6-day peripheral blood T cell proliferative response to native human PDC also responded, in a MHC class II-restricted fashion, to biochemically purified PDC-E2 and E3BP (which co-purify) (9/10 positive (SI > 2.76), mean SI 5.74 +/- 5.04 (PDC-E2/E3BP) versus 6.67 +/- 3.84 (PDC), P = NS), implying that the important PBC-specific T cell epitopes are contained within the PDC-E2 or E3BP components of PDC. Only a minority of patients responsive to PDC, however, responded to either lipoylated recombinant PDC-E2 ILD (4/10 positive, mean SI 1.98 +/- 1.24, P < 0.005 versus PDC response) or lipoylated p163 (4/12 positive, mean SI 1.90 +/- 1.58, P < 0.001). The lipoylation state did not affect the T cell response to either ILD or p163. Our findings suggest that in some UK patients with PBC there are immunodominant T cell autoepitopes within PDC-E2/E3BP which are outside the ILD of PDC-E2.

Autoantigens↗

PubMed1999

Case report: oral antioxidant therapy for the treatment of primary biliary cirrhosis: a pilot study.

BACKGROUND: The symptoms of the chronic cholestatic liver disease primary biliary cirrhosis (PBC), in particular fatigue and chronic pruritus, adversely affect quality of life and respond only poorly to treatment. Recent studies have suggested that oxidative stress may play a role in tissue damage in cholestatic liver disease and may contribute to symptoms, such as fatigue. We have, therefore, examined, in an open-label pilot study, the therapeutic effects of antioxidant medication on the biochemistry and symptomatology of PBC. METHODS: Patients were randomized to 3 months treatment with a compound antioxidant vitamin preparation (Bio-Antox), four tablets daily (n = 11, group 1), or the combination of Bio-Quinone Q10 (100 mg) with Bio-Antox (n = 13, group 2). Biochemical and symptomatic responses were assessed at 3 months. RESULTS: Significant improvement in both pruritus and fatigue was seen in the patients in group 2. Mean itch visual analogue score improved from 2.4 +/- 3.0 to 0.4 +/- 0.7 post therapy (P < 0.05) while mean night itch severity score improved from 2.6 +/- 1.9 to 1.3 +/- 0.7 (P < 0.05). Nine of 13 of these patients reported less fatigue, while 10/13 showed an improvement in at least one domain of their Fisk Fatigue Severity Score. No significant improvement in itch and only limited improvement in fatigue were seen in the patients in group 1. No change in biochemical parameters was seen in either group. CONCLUSIONS: Antioxidant therapy, as a combination of Bio-Antox and Bio-Quinone Q10, may improve the pruritus and fatigue of PBC. This combination of therapy should be investigated further in a double-blind, placebo-controlled trial.

Antioxidants↗

PubMed1999

Genetic susceptibility to primary biliary cirrhosis.

Family studies suggest that genetic factors play a role in determining susceptibility to primary biliary cirrhosis (PBC). A number of polymorphic genes with small and additive effects may thus encode factors predisposing to this 'polygenic' disease. All the published data on genetic predisposition to PBC have been obtained from association studies, based on comparison of the frequency of an allele in unrelated affected and unaffected individuals from a population; however, many studies have examined only small datasets. There is evidence from several different populations to support a role for the major histocompatibility complex (MHC) class II antigen, HLA DR8, in increased risk of PBC. Other 'candidate' genes, selected on the basis of postulated mechanisms of breakdown of self-tolerance, are now beginning to be tested in association studies, including cytokines and immunomodulatory molecules. These studies and other approaches to identifying genes that confer susceptibility to an autoimmune disorder, exemplified by PBC, are discussed.

Autoimmune Diseases↗

PubMed1999

The CLO test in the UK: inappropriate reading and missed results.

BACKGROUND: In endoscopy units, the CLO test is frequently used to detect Helicobacter pylori (H. pylori). Informal survey suggested that practice deviated from that recommended, with little account taken of possible confounders such as acid-suppressing medication. OBJECTIVES: To determine the influence of reading time and acid suppression on CLO tests and to estimate impact on test results in UK endoscopy units. DESIGN: Survey of use of CLO tests. Prospective study of time to positivity and concurrent medication in CLO tests from 782 patients. SETTING: Forty-eight endoscopy units throughout the UK, and a district hospital endoscopy unit. PARTICIPANTS: Eighteen endoscopy units in the old Northern Region, and a random sample of 30 other UK units. MAIN OUTCOME MEASURES: Time of reading of CLO tests in UK units, and time to positivity of CLO tests in one hospital. RESULTS: Endoscopy units most frequently used CLO tests to assess H. pylori colonization, with marked differences in the times when tests were read. Nineteen out of 37 units discarded tests considerably earlier than the recommended 24 h. Over 20% of CLO tests became positive more than 2 h after collection, with 11% taking 24 h to change colour. Acid-suppressing medication prolonged time to positivity. CONCLUSIONS: The majority of endoscopy units read tests earlier than recommended. Acid-suppressing medication delays the development of CLO tests and may increase numbers of false-negative tests. Endoscopy units should read tests at 24 h and preferably test patients off ulcer healing medication.

Evaluation Studies as Topic↗

PubMed1999

Cancer risk in primary biliary cirrhosis: a study in northern England.

BACKGROUND: Suggestions that breast cancer may be more common in patients with primary biliary cirrhosis (PBC) have been challenged. It has recently been proposed that total cancer rates may be higher in patients with PBC, as well as liver cancers. AIMS: To investigate these proposals on a strictly defined case series. SUBJECTS: A total of 769 prevalent or incident PBC patients with "definite" or "probable" disease detected in a defined area of the north-east of England during 1987-94. METHODS: Cancer events and deaths were identified by obtaining information from one or more of the following sources: Office for National Statistics (ONS) Central Registers, Regional Cancer Registry, and clinical case records. Standardised cancer incidence (SIR) and mortality ratios (SMR) were calculated using the local region as the standard population. RESULTS: There were 97 cancer events during 1987-96. SIR from cancer registrations for all cancers was 1.7 (95% confidence interval (CI) 1.3 to 2.2), for liver cancer was 74 (95% CI 32 to 146), and for breast cancer was 1.1 (95% CI 0.4 to 2.4). SMR for all cancers was 1. 8 (95% CI 1.4 to 2.4), for liver cancer was 39 (95% CI 20 to 68), and for breast cancer was 0.4 (95% 0.1 to 1.6). The results were similar after excluding the first year of follow up after PBC diagnosis. CONCLUSIONS: There was some evidence of a small increase in overall cancer incidence and mortality in PBC patients. With the exception of liver cancer, it is unlikely that there is a high excess incidence for PBC patients from any cancer at a particular site, and specifically breast cancer.

Adolescent↗