Sex and age are determinants of the clinical phenotype of primary biliary cirrhosis and response to ursodeoxycholic Acid
Open accessAbstract
Unlabelled BACKGROUND, & AIMS: Studies of primary biliary cirrhosis (PBC) phenotypes largely have been performed using small and selected populations. Study size has precluded investigation of important disease subgroups, such as men and young patients. We used a national patient cohort to obtain a better picture of PBC phenotypes.Methods We performed a cross-sectional study using the United Kingdom-PBC, patient cohort. Comprehensive data were collected for 2353 patients on diagnosis reports, response to therapy with ursodeoxycholic acid (UDCA), laboratory results, and symptom impact (assessed using the PBC-40 and other related measures).Results Seventy-nine percent of the patients reported current UDCA, therapy, with 80% meeting Paris response criteria. Men were significantly less likely to have responded to UDCA than women (72% vs 80% response rate; P < .05); male sex was an independent predictor of nonresponse on multivariate analysis. Age at diagnosis was associated strongly and independently with response to UDCA; response rates ranged from 90% among patients who presented with PBC when they were older than age 70, to less than 50% for those younger than age 30 (P < .0001). Patients who presented at younger ages also were significantly more likely not to respond to UDCA therapy, based on alanine aminotransferase and aspartate aminotransferase response criteria, and more likely to report fatigue and pruritus. Women had mean fatigue scores 32% higher than men's (P < .0001). The increase in fatigue severity in women was related strongly (r = 0.58; P < .0001) to higher levels of autonomic symptoms (P < .0001).Conclusions Among patients with PBC, response to UDCA, treatment and symptoms are related to sex and age at presentation, with the lowest response rates and highest levels of symptoms in women presenting at younger than age 50. Increased severity of fatigue in women is related to increased autonomic symptoms, making dysautonomia a plausible therapeutic target.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Data from the UK-PBC patient cohort have shown that there is significant variation in management between centres and individual clinicians.
“Data from the UK-PBC patient cohort have shown that there is significant variation in management between centres and individual clinicians.12”
From The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines (2018) · cites this paper as [12]
The Results (page unavailable) report no significant difference in UDCA use between specialist and nonspecialist centres (81% versus 80%) and similar response rates. The Discussion likewise says patients in the two settings were equally likely to receive UDCA. The paper does not assess variation between individual clinicians. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredMale sex is linked to later diagnosis, more advanced disease at presentation, poorer biochemical response to UDCA, and higher HCC risk.
“Male sex is associated with later diagnosis, more advanced disease at presentation, poorer biochemical response to UDCA therapy, and higher risk of developing hepatocellular carcinoma (HCC) [6,8,65].”
From EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. (2017) · cites this paper as [6]
The Results and Discussion (page not provided) report that men with PBC presented at an older age, had signs suggesting more advanced disease and delayed diagnosis, and were less likely to meet UDCA response criteria. The passages found do not address whether men have a higher risk of developing HCC, so this source does not support that part of the sentence. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPBC is chronic and often progressive, leading to end-stage liver disease and related complications.
“The disease is chronic and often progressive, resulting in end-stage liver disease and its associated complications [6][7][8].”
From EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. (2017) · cites this paper as [6]
The Additional information section defines PBC-related failure to include liver transplantation or death from liver failure, supporting the possibility of severe outcomes. But the Discussion describes a potentially aggressive course particularly in younger patients, while characterizing the typical patient's course as relatively benign; it does not establish that PBC is often progressive to end-stage disease. Page numbers were not available in our copy. (LLM, conf=0.83)
Experimental — accuracy not yet measuredPBC is chronic and often progressive, leading to end-stage liver disease and its complications.
“The disease is chronic and often progressive, resulting in end-stage liver disease and its associated complications [6][7][8].”
From EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. (2017) · cites this paper as [6]
The Additional information section (page not provided) treats PBC-related liver failure and liver transplantation as possible outcomes, supporting the claim that the disease can reach an advanced stage. The Discussion (page not provided) emphasizes variation in prognosis and describes a potentially more aggressive course in some younger patients; it does not establish that progression is often the case or describe the associated complications. (LLM, conf=0.82)
Experimental — accuracy not yet measuredMale sex is associated with later diagnosis, more advanced disease at presentation, poorer biochemical response to UDCA, and higher risk of hepatocellular carcinoma.
“Male sex is associated with later diagnosis, more advanced disease at presentation, poorer biochemical response to UDCA therapy, and higher risk of developing hepatocellular carcinoma (HCC) [6,8,65].”
From EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. (2017) · cites this paper as [6]
The Results and Discussion (page not provided) report that men with PBC presented at an older age with signs of more advanced disease, suggest delayed diagnosis, and found a lower rate of adequate UDCA response. Our copy does not report that men have a higher risk of developing hepatocellular carcinoma; searches for that term and HCC did not identify supporting passages. (LLM, conf=0.88)
Experimental — accuracy not yet measured
There is no evidence that UDCA affects pruritus, while higher doses of OCA can worsen it.
“There is no evidence to suggest that UDCA has any effect on pruritus [6,127], whilst OCA at higher doses can exacerbate it.”
From EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. (2017) · cites this paper as [6]
Table 2 reports no significant difference in current pruritus between patients not receiving UDCA and those responding to it. But the Results also report significantly worse pruritus among UDCA nonresponders, and the study does not establish that UDCA has no effect on pruritus. The citation is attached to the UDCA clause, not the separate OCA claim. (LLM, conf=0.82)
Experimental — accuracy not yet measuredFatigue is not related to liver disease severity except in very end-stage patients, and it does not respond to UDCA or OCA.
“Fatigue is not related to severity of liver disease, with the exception of very end-stage patients where it is the norm [221], and it is not responsive to UDCA or OCA therapy [6,131].”
From EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. (2017) · cites this paper as [6]
The Results report that fatigue severity was not associated with biochemical response to UDCA, and Table 2 shows no significant difference in fatigue scores between UDCA-treated and untreated patients. These comparisons support the UDCA portion indirectly, but do not establish whether an individual's fatigue changes with treatment; the paper provides no evidence about fatigue response to OCA. The end-stage exception is attached to a different citation in the citing sentence. (LLM, conf=0.86)
Experimental — accuracy not yet measuredMore than 80% of UDCA-treated patients continue to experience symptoms, especially fatigue and cognitive symptoms.
“>80% continue to experience symptoms, especially fatigue and cognitive symptoms that are seemingly not modified by any current intervention.2 3 9 17”
From Optimising Primary thErapy in pRimAry biliary cholangitis (OPERA): protocol for a randomised, double-blind, placebo-controlled trial of enhanced primary therapy with obeticholic acid (2026) · cites this paper as [2]
Table 2 reports fatigue and cognitive symptom scores among UDCA-treated patients, and the Results state that fatigue severity was not associated with biochemical response to UDCA. The paper does not establish that more than 80% of treated patients remain symptomatic or that no current intervention modifies those symptoms. (LLM, conf=0.82)
Experimental — accuracy not yet measuredAt a population level, UDCA improves serum liver biochemical markers, delays liver transplantation and increases life expectancy.
“At a population level, UDCA improves serum liver biochemical markers, delays liver transplantation and increases life expectancy.21013”
From Optimising Primary thErapy in pRimAry biliary cholangitis (OPERA): protocol for a randomised, double-blind, placebo-controlled trial of enhanced primary therapy with obeticholic acid (2026) · cites this paper as [2]
The Results (page unavailable) report biochemical responses to UDCA and worse liver biochemistry in untreated patients than in UDCA responders. Additional information, Figure 3 (page unavailable), shows better outcomes for responders on a measure combining transplantation, liver-related death, and high bilirubin. It does not establish that UDCA itself delays transplantation or increases life expectancy at a population level. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe majority of patients diagnosed today are asymptomatic at diagnosis and nearly 90% do not have fibrosis when first identified.
“The majority of patients diagnosed today are asymptomatic at diagnosis and one contemporary series showed that nearly 90% do not have fibrosis when first identified (although others have shown higher rates potentially reflecting case mix).11 12 26 27”
From The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines (2018) · cites this paper as [12]
The Discussion (page not available) says that most patients were older at diagnosis and had a low symptom burden; the paper also describes the typical patient as presenting with relatively few symptoms. That does not establish that a majority were asymptomatic at diagnosis. A search of the full-text copy found no finding that nearly 90% lacked fibrosis when first identified. (LLM, conf=0.83)
Experimental — accuracy not yet measuredThe symptoms of PBC typically do not correlate with disease severity and do not improve with UDCA therapy.
“The symptoms of PBC typically do not correlate with disease severity and do not improve with UDCA therapy.12”
From The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines (2018) · cites this paper as [12]
The Results (page unavailable) report that fatigue severity was not associated with biochemical measures, supporting that part of the claim. But pruritus was higher in UDCA nonresponders and associated with alkaline phosphatase, so the claim is too broad for PBC symptoms generally. The study compares symptoms across treatment-response groups; it does not show whether symptoms improve after starting UDCA. (LLM, conf=0.88)
Experimental — accuracy not yet measuredFatigue is, with the exception of very endstage patients where it is the norm, not related to severity of liver disease and is not responsive to UDCA therapy.
“Fatigue is, with the exception of very endstage patients where it is the norm,211 not related to severity of liver disease and is not responsive to UDCA therapy.12”
From The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines (2018) · cites this paper as [12]
The Results (page unavailable) report that fatigue severity was not associated with any biochemical parameter, supporting the claim about liver-disease severity. Table 2 (page unavailable) shows no significant difference in fatigue scores between UDCA-treated and untreated patients, or between biochemical responders and nonresponders. Those comparisons do not directly establish that fatigue cannot improve with UDCA therapy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredFatigue is not specific to PBC, is frequently reported by patients (over 50%) and when severe (20%) is a significant cause of QoL impairment.
“Although fatigue is not specific to PBC, it is frequently reported by patients (over 50%) and when severe, as it is in 20% of patients, is a significant cause of QoL impairment.12 171 205–208”
From The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines (2018) · cites this paper as [12]
The Results describe fatigue in patients with PBC, and the PBC-40 section identifies fatigue as a domain of a quality-of-life measure (page numbers not provided). The passages do not establish that fatigue is nonspecific to PBC, occurs in over 50% of patients, is severe in 20%, or causes significant quality-of-life impairment. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThere is limited evidence to suggest that UDCA has any effect on pruritus.
“There is limited evidence to suggest that UDCA has any effect on pruritus.12 179”
From The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines (2018) · cites this paper as [12]
Table 2 reports similar current-pruritus scores for UDCA responders and patients reporting no UDCA treatment, which is consistent with limited evidence of a treatment effect. The Results also report worse pruritus among UDCA nonresponders, but these observational comparisons do not establish whether UDCA itself affects pruritus or assess the overall strength of evidence for such an effect. (LLM, conf=0.76)
Experimental — accuracy not yet measuredParis 2 criteria have been recognized as relevant predictors of clinical outcomes in several independent populations of patients with primary biliary cholangitis.
“Patients were selected on the basis of Paris 2 criteria, 15 which have been recognized as relevant predictors of clinical outcomes in several independent populations of patients with primary biliary cholangitis.24,25”
From A Placebo-Controlled Trial of Bezafibrate in Primary Biliary Cholangitis (2018) · cites this paper as [24]
The Results (page unavailable) state that Paris II, along with three other UDCA-response criteria, predicted outcomes in the paper’s extended-data subgroup. The paper reports this finding in one UK-PBC cohort, not in several independent patient populations; it also found Paris I discriminated prognosis best. (LLM, conf=0.87)
Experimental — accuracy not yet measuredAn abnormally elevated level of alkaline phosphatase persists in many patients, and mortality is significantly higher among these patients than in the general population.
“However, an abnormally elevated level of alkaline phosphatase persists in many patients, and mortality is significantly higher among these patients than in the general population; therefore, there is an unmet need for additional therapeutic options for patients with primary biliary cholangitis. 9”
From A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis (2016) · cites this paper as [9]
The clinical-characteristics table (page not listed) reports an alkaline phosphatase level of 1.8 times the upper limit of normal in the cohort, supporting the point that elevated levels remain common. Figure 3 (Additional information; page not listed) finds a significant difference in a composite outcome between UDCA responders and nonresponders, but it does not compare mortality in patients with elevated alkaline phosphatase against mortality in the general population. (LLM, conf=0.84)
Experimental — accuracy not yet measuredHigher levels of alkaline phosphatase and bilirubin correlate with disease progression, and lower levels are predictive of survival without the need for liver transplantation.
“Higher levels of alkaline phosphatase and bilirubin levels correlate with disease progression, and lower levels are predictive of survival without the need for liver transplantation. 9,10”
From A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis (2016) · cites this paper as [9]
Table 3 reports that lower baseline alkaline phosphatase and bilirubin independently predicted response to UDCA. The Figure 3 caption reports that treatment-response criteria incorporating these measures distinguished patients by a composite outcome including liver transplantation and PBC-related death. The paper does not establish that the two measures individually predict transplant-free survival or directly correlate with disease progression as broadly stated. (LLM, conf=0.83)
Experimental — accuracy not yet measuredPatients diagnosed younger than 45 are often symptomatic and less likely to respond well to standard UDCA treatment.
“Patients who present at a younger age (\45 years) are often symptomatic and less likely to respond well to standard treatment with UDCA [6].”
From EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. (2017) · cites this paper as [6]
Response to UDCA is variable, and incomplete response is associated with increased risk of death from PBC or need for liver transplantation.
“Response to UDCA is variable, and incomplete response is associated with increased risk of death from PBC or need for liver transplantation.11–18”
From The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines (2018) · cites this paper as [12]
There are potentially important differences in the clinical expression of PBC between men and women and between older and younger patients.
“There are potentially important differences in the clinical expression of PBC between men and women and between older and younger patients, although the basic approach to management is the same in all demographic groups.12”
From The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines (2018) · cites this paper as [12]
UK data suggest that PBC is diagnosed at a later stage in men, potentially reflecting perception bias among clinicians.
“UK data suggest that PBC is diagnosed at a later stage in men, potentially reflecting perception bias among clinicians.12”
From The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines (2018) · cites this paper as [12]
There is significant variation in how PBC patients are managed between centres and clinicians.
“Currently, there is significant variation in patient management between centres and individual clinicians [6].”
From EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. (2017) · cites this paper as [6]
The Results report similar UDCA use in specialist and nonspecialist units (81% versus 80%), and the Discussion likewise says patients in those settings were equally likely to receive UDCA. Our copy does not assess variation among individual centres or clinicians, so it does not establish the claimed significant variation in management. (LLM, conf=0.72)
Experimental — accuracy not yet measuredThe model was adjusted for age, gender, and UDCA dose because these factors have been shown to influence biochemical response in PBC.
“We adjusted the model for confounding factors, including age, gender, and UDCA dose, because these factors have been shown to influence biochemical response in PBC.23,24”
From Combination of fibrates with obeticholic acid is able to normalise biochemical liver tests in patients with difficult‐to‐treat primary biliary cholangitis (2021) · cites this paper as [23]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 23 · Cited by 386
- Authors
- Carbone, M., Mells, G. F., Pells, G., Dawwas, M. F., Newton, J. L., Heneghan, M. A., Neuberger, J. M., Day, D. B., Ducker, S. J., Sandford, R. N., Alexander, G. J., & Jones, D. E. J.
- Affiliations
- University of Cambridge (GB)
- Newcastle University (GB)
- National Institute for Health and Care Research (GB)
- National Health Service (GB)
- Queen Elizabeth Hospital Birmingham (GB)
- Corresponding author
- Jones, David E.J.
- ORCID
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 144
- Issue
- 3
- Pages
- 560-569.e7
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2032058959
- Semantic Scholar
- 70799827d7fce38ef875e0478d9250ebc076904a
- Cited by
- 386
- References
- 23
- Citations by year
- 2026: 19 · 2025: 15 · 2024: 24 · 2023: 29 · 2022: 37 · 2021: 42 · 2020: 34 · 2019: 33 · 2018: 47 · 2017: 37 · 2016: 17 · 2015: 25 · 2014: 17 · 2013: 10
- FWCI
- 10.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- University of Cambridge
- Wellcome Trust
- Newcastle University
- Medical Research Council
- Newcastle upon Tyne Hospitals NHS Foundation Trust
- Isaac Newton Trust
- NIHR Newcastle Biomedical Research Centre
- National Institute for Health Research
- Topics
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- primary biliary cirrhosis, ursodeoxycholic acid, treatment response, sex differences, age at diagnosis, clinical phenotype, fatigue, pruritus, autonomic symptoms, autonomic dysfunction, young patients
- MeSH terms
- Adult, Age Factors, Aged, Aged, 80 and over, Female, United Kingdom, Humans, Liver Cirrhosis, Biliary, Male, Middle Aged, Sex Factors, Ursodeoxycholic Acid, Treatment Outcome, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
