The DOI matches its Crossref record; 279 of the 279 references it cites were found in a registry or an index; 18 of the 48 sources its claims cite were checked for support.
EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis.
Open accessAbstract
Clinical practice guidelines summarising diagnosis, risk stratification, and management of PBC including ursodeoxycholic acid, obeticholic acid, and off-label therapies.
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Claims the paper makes
18 of 48 cited sources checked · 7 supported · 0 flagged · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“Serum bilirubin has been recognised since the 1970s as a major predictor of poor outcome in PBC [72,7].”
What the sources say
- Supportedcites [72] 72. Shapiro JM, Smith H, Schaffner F. Serum bilirubin: a prognostic factor in primary biliary cirrhosis. Gut 1979;20:137-140. source
The 1979 paper’s Abstract (p. 137) identifies serum bilirubin as a predictor of prognosis in primary biliary cirrhosis. Its Presentation section reports that higher successive bilirubin levels were associated with shorter predicted survival, supporting the claim about poor outcome. (LLM, conf=0.93)
- Supportedcites [7] 7. Lammers WJ, van Buuren HR, Hirschfield GM, Janssen HL, Invernizzi P, Mason AL, et al. Levels of alkaline phosphatase and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis: an international follow-up study. Gastroenterology 2014;147:1338-1349. source
The introduction (p. 2) calls serum bilirubin a well-established independent predictor of prognosis in PBC. Its cited references (p. 11) include a 1979 study titled “Serum bilirubin: a prognostic factor in primary biliary cirrhosis,” supporting the 1970s timeframe. (LLM, conf=0.91)
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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].”
What the sources say
- Partly supportedcites [6] 6. Carbone M, Mells GF, Pells G, Dawwas MF, Newton JL, Heneghan MA, et al. Sex and age are determinants of the clinical phenotype of primary biliary cirrhosis and response to ursodeoxycholic Acid. Gastroenterology 2013;144:560-569. sourceExperimental — accuracy not yet measured
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)
- Not checked — no full text of the sourcecites [8] 8. Trivedi PJ, Lammers WJ, van Buuren HR, Pares A, Floreani A, Janssen HL, et al. Stratification of hepatocellular carcinoma risk in primary biliary cirrhosis: a multicentre international study. Gut 2016;65:321-329. source
- Not checked — no full text of the sourcecites [65] 65. Cheung A, Lammers WJ, Hirschfield GM, Invernizzi P, Mason A, Ponsioen CY, et al. Age, bilirubin and albumin, regardless of sex, are the strongest independent predictors of biochemical response and transplantation-free survival in patients with primary biliary cirrhosis. J Hepatol 2015;62: S798-S799. source
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Patients who present at a younger age (\45 years) are often symptomatic and less likely to respond well to standard treatment with UDCA [6].”
What the sources say
- Supportedcites [6] 6. Carbone M, Mells GF, Pells G, Dawwas MF, Newton JL, Heneghan MA, et al. Sex and age are determinants of the clinical phenotype of primary biliary cirrhosis and response to ursodeoxycholic Acid. Gastroenterology 2013;144:560-569. source
The Results and Discussion (page not available in our copy) report that patients presenting at younger ages were more likely to have fatigue and pruritus and less likely to respond to UDCA. The paper specifically identifies age 45 as a response threshold for women; the age-related response effect was weaker in men. (LLM, conf=0.88)
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The disease is chronic and often progressive, resulting in end-stage liver disease and its associated complications [6][7][8].”
What the sources say
- Partly supportedcites [6] 6. Carbone M, Mells GF, Pells G, Dawwas MF, Newton JL, Heneghan MA, et al. Sex and age are determinants of the clinical phenotype of primary biliary cirrhosis and response to ursodeoxycholic Acid. Gastroenterology 2013;144:560-569. sourceExperimental — accuracy not yet measured
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)
- Supportedcites [7] 7. Lammers WJ, van Buuren HR, Hirschfield GM, Janssen HL, Invernizzi P, Mason AL, et al. Levels of alkaline phosphatase and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis: an international follow-up study. Gastroenterology 2014;147:1338-1349. source
The introductory passage (p. 1) describes PBC as a chronic, slowly progressive disease that typically progresses to cirrhosis, which may lead to complications from liver failure. This supports the cited sentence’s description of progression to end-stage liver disease and associated complications. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [8] 8. Trivedi PJ, Lammers WJ, van Buuren HR, Pares A, Floreani A, Janssen HL, et al. Stratification of hepatocellular carcinoma risk in primary biliary cirrhosis: a multicentre international study. Gut 2016;65:321-329. source
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“PBC recurrence has been reported in 20% of patients on average [253,258] but the rate of histological recurrence is likely higher [259].”
What the sources say
- Partly supportedcites [253] 253. Carbone M, Neuberger JM. Autoimmune liver disease, autoimmunity and liver transplantation. J Hepatol 2014;60:210-223. sourceExperimental — accuracy not yet measured
In the section on recurrence after liver transplantation (page unavailable), the paper reports recurrent PBC prevalence of 0–35% and 10-year incidence of 21–37%, but does not give a 20% average. It says recurrence can occur with normal liver tests and that biopsy practices affect reported rates, supporting the possibility of missed histological recurrence without quantifying how much higher its rate is. (LLM, conf=0.82)
- Not checked — no full text of the sourcecites [258] 258. Silveira MG, Talwalkar JA, Lindor KD, Wiesner RH. Recurrent primary biliary cirrhosis after liver transplantation. Am J Transplant 2010;10:720-726. source
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Treatment with OCA is associated with a dose dependent exacerbation in pruritus, leading to treatment discontinuation in 4-10% of patients [130,131].”
What the sources say
- Partly supportedcites [130] 130. Hirschfield GM, Mason A, Luketic V, Lindor K, Gordon SC, Mayo M, et al. Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid. Gastroenterology 2015;148:751-761. sourceExperimental — accuracy not yet measured
The Discussion describes pruritus as clearly OCA dose-related, and Study Patients reports that pruritus was the principal reason for discontinuation (10%). The cited 4–10% range is not established by these passages: Adverse Events reports 13% discontinuation due to pruritus in the open-label extension. Page numbers were not available in our copy. (LLM, conf=0.88)
- Supportedcites [131] 131. Nevens F, Andreone P, Mazzella G, Strasser SI, Bowlus C, Invernizzi P, et al. A placebo-controlled trial of obeticholic acid in primary biliary cholangitis. N Engl J Med 2016;375:631-643. source
The Safety and Side Effects section reports more pruritus in the 5–10 mg and 10 mg groups than in the placebo group, with the highest incidence at 10 mg. It also reports that 8 of 217 patients (4%) withdrew because of pruritus overall, while 7 patients (10%) in the 10 mg group discontinued treatment for that reason. The 5–10 mg group's discontinuation rate was lower, at 1%. (LLM, conf=0.88)
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“PBC-specific ANA (antibodies against gp210 and sp100 antigens) are more frequently observed in patients with severe PBC and their presence may also be predictive of an unfavourable course, irrespective of serum bilirubin [75][76][77]63,78].”
What the sources say
- Not checked — no full text of the sourcecites [75] 75. Muratori P, Muratori L, Ferrari R, Cassani F, Bianchi G, Lenzi M, et al. Characterization and clinical impact of antinuclear antibodies in primary biliary cirrhosis. Am J Gastroenterol 2003;98:431-437. source
- Partly supportedcites [76] 76. Rigopoulou EI, Davies ET, Pares A, Zachou K, Liaskos C, Bogdanos DP, et al. Prevalence and clinical significance of isotype specific antinuclear antibod- ies in primary biliary cirrhosis. Gut 2005;54:528-532. sourceExperimental — accuracy not yet measured
The Results and Discussion (page not available in our copy) associate PBC-specific ANA with more severe disease and worse outcomes, particularly for the multiple-nuclear-dot pattern. The study tested immunofluorescence patterns rather than separately establishing these findings for anti-gp210 and anti-sp100, and it does not show that the outcome association is independent of serum bilirubin. (LLM, conf=0.88)
- Partly supportedcites [77] 77. Wesierska-Gadek J, Penner E, Battezzati PM, Selmi C, Zuin M, Hitchman E, et al. Correlation of initial autoantibody profile and clinical outcome in primary biliary cirrhosis. Hepatology 2006;43:1135-1144. sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) identifies gp210 and Sp100 as PBC-specific ANA targets and says PBC-specific ANA correlate with disease severity in cross-sectional studies. The Results (page unavailable) link anti-NPC antibodies, including anti-gp210, to poorer outcomes, but do not establish that anti-Sp100 predicts outcome. Anti-NPC added independent prognostic information only in patients with baseline bilirubin below 1 mg/dL, so the claim is too broad about prediction irrespective of bilirubin. (LLM, conf=0.88)
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Treatment failure must be defined on validated surrogate endpoints to account for the slow progression of disease, i.e. endpoints that have significant reproducible prognostic performance in different cohorts of patients [100].”
What the sources say
- Partly supportedcites [100] 100. Silveira MG, Brunt EM, Heathcote J, Gores GJ, Lindor KD, Mayo MJ. American Association for the Study of Liver Diseases endpoints conference: design and endpoints for clinical trials in primary biliary cirrhosis. Hepatology 2010;52:349-359. sourceExperimental — accuracy not yet measured
The Endpoints of Clinical Trials in PBC section says slow progression makes death or transplantation impractical trial endpoints, and the Biochemical Markers section recommends biochemical markers as primary endpoints. But the paper does not say treatment failure must be defined by validated surrogates with reproducible prognostic performance across different cohorts; it allows several ways to assess response. Page numbers were not available in our copy. (LLM, conf=0.85)
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“continuous scoring systems incorporating both measures of treatment response and parameters of disease severity [106,107].Thus, both the GLOBE score and the UK-PBC score have shown better performance for the prediction of death or liver transplantation than the Paris-I criteria, which have the best performance among binary models.”
What the sources say
- Partly supportedcites [106] 106. Lammers WJ, Hirschfield GM, Corpechot C, Nevens F, Lindor KD, Janssen HL, et al. Development and validation of a scoring system to predict outcomes of patients with primary biliary cirrhosis receiving ursodeoxycholic acid therapy. Gastroenterology 2015;149:1804-1812. sourceExperimental — accuracy not yet measured
The Performance of the GLOBE Score Compared With Other Criteria section says GLOBE discriminated outcomes better than the earlier criteria; Table 3 reports higher C-statistics for GLOBE than Paris-1 and the other binary criteria. The paper also describes Paris-1 as generally having the best predictability among those criteria. It does not evaluate the UK-PBC score, so it cannot support that score’s claimed superiority to Paris-1; its mention of the UK-PBC consortium is not a comparison of scores. (LLM, conf=0.88)
- Partly supportedcites [107] 107. Carbone M, Sharp SJ, Flack S, Paximadas D, Spiess K, Adgey C, et al. The UK- PBC risk scores: Derivation and validation of a scoring system for long-term prediction of end-stage liver disease in primary biliary cirrhosis. Hepatol- ogy 2016;63:930-950. sourceExperimental — accuracy not yet measured
The Validation of the PBC Risk Score section reports higher AUCs for UK-PBC than for Paris I, and Paris I has the highest AUCs among the four binary models compared. The paper does not report a GLOBE-score comparison, so it does not support that part of the claim. (LLM, conf=0.88)
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The enhanced liver fibrosis (ELF) score, which is computed from the simultaneous measurements of serum concentrations of hyaluronic acid, procollagen III peptide and tissue inhibitor of metalloproteinase 1, have shown similar predictive capacity [74].”
What the sources say
- Supportedcites [74] 74. Mayo MJ, Parkes J, Adams-Huet B, Combes B, Mills AS, Markin RS, et al. Prediction of clinical outcomes in primary biliary cirrhosis by serum enhanced liver fibrosis assay. Hepatology 2008;48:1549-1557. source
The Methods identify hyaluronic acid, procollagen type III N-terminal propeptide, and TIMP-1 as components of the ELF assay. The Results report no statistically significant difference between ELF and histological staging in predicting clinical outcomes in patients with primary biliary cirrhosis, supporting similar predictive capacity in that comparison. (LLM, conf=0.90)
- Supported
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“A diagnosis of primary biliary cholangitis is made if patients meet at least two of the following criteria: have biochemical evidence of chronic cholestasis, positive anti-mitochondrial antibodies in sera, and histological features compatible with primary biliary cholangitis.[3][4][5]”
From Primary biliary cholangitis. (2024) · cites this paper as [3]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“the treatment response to ursodeoxycholic acid was incomplete in about 20-40% of patients with primary biliary cholangitis after 1 year, as judged by various biochemical criteria, either binary or continuously.3”
From Primary biliary cholangitis. (2024) · cites this paper as [3]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Clinically, primary biliary cholangitis is characterised by persistent elevation of cholestatic liver enzymes, including alkaline phosphatase and gammaglutamyl transpeptidase (GGT), and detection of antimitochondrial antibodies or primary biliary cholangitis-specific anti-nuclear antibodies (anti-sp100 or anti-gp210).[3][4][5]”
From Primary biliary cholangitis. (2024) · cites this paper as [3]
The cited source says what the claim attributes to it.
In the citing paper
“Non-invasive liver stiffness measurement (LSM) has proven useful as an alternative to invasive liver biopsy for the evaluation of liver fibrosis, and LSM using transient elastography is recommended at the time of diagnosis.3,4,55”
From Primary biliary cholangitis. (2024) · cites this paper as [3]
The cited source says what the claim attributes to it.
In the citing paper
“Clinical practice guidelines from the European Association for the Study of the Liver, the American Association for the Study of Liver Diseases (AASLD), and the Asian-Pacific Association for the Study of the Liver recommend ursodeoxycholic acid treatment (13-15 mg/kg per day) for all patients with primary biliary cholangitis and elevated cholestatic enzymes.[3][4][5]”
From Primary biliary cholangitis. (2024) · cites this paper as [3]
The cited source says what the claim attributes to it.
In the citing paper
“Ursodeoxycholic acid is standard-of-care treatment for primary biliary cholangitis.”
From Primary biliary cholangitis. (2024) · cites this paper as [3]
The cited source says what the claim attributes to it.
In the citing paper
“For treatment, clinical indices have been developed to establish ursodeoxycholic acid treatment response at 1-2 years by biochemical tests, either binary or continuously.3”
From Primary biliary cholangitis. (2024) · cites this paper as [3]
The cited source says what the claim attributes to it.
In the citing paper
“In addition, the liver stiffness measurement (LSM) in stratifying the risk for progression has been confirmed.3,4,55”
From Primary biliary cholangitis. (2024) · cites this paper as [3]
The cited source says what the claim attributes to it.
In the citing paper
“Ursodeoxycholic acid, a hydrophilic bile acid with choleretic and liver-protective properties, is currently the standard firstline therapy for primary biliary cholangitis.2,3”
From A Placebo-Controlled Trial of Bezafibrate in Primary Biliary Cholangitis (2018) · cites this paper as [2]
In the citing paper
“For sertraline as fourth-line treatment, no sufficient data for sclerosing cholangitis-associated itch exist.20,51”
From EASL Clinical Practice Guidelines on sclerosing cholangitis (2022) · cites this paper as [51]
In the citing paper
“Rifampicin was so far regarded as the most effective evidence-based treatment of cholestasis-associated pruritus, but it may induce drug-induced hepatitis after 4-12 weeks in up to 12% of cholestatic patients while the first 2 weeks are regarded as safe.20,51”
From EASL Clinical Practice Guidelines on sclerosing cholangitis (2022) · cites this paper as [51]
In the citing paper
“The evidence for the antipruritic effectiveness of the non-absorbable anion exchange resin cholestyramine in sclerosing cholangitis is limited when compared to PBC, 20,51 and that of the more potent anion exchange resin colesevelam is non-existent.217”
From EASL Clinical Practice Guidelines on sclerosing cholangitis (2022) · cites this paper as [51]
In the citing paper
“Abdominal discomfort | 20,51”
From EASL Clinical Practice Guidelines on sclerosing cholangitis (2022) · cites this paper as [51]
In the citing paper
“| No evidence for PSC | Sertraline (50-75 mg/d) | | 20,51 |”
From EASL Clinical Practice Guidelines on sclerosing cholangitis (2022) · cites this paper as [51]
In the citing paper
“| No evidence for PSC | Anion exchange resins (cholestyramine [4 g once to four | Abdominal discomfort | 20,51 |”
From EASL Clinical Practice Guidelines on sclerosing cholangitis (2022) · cites this paper as [51]
In the citing paper
“| 2 nd line | Rifampicin (150-300 mg/d) | Hepatitis | 20,51 |”
From EASL Clinical Practice Guidelines on sclerosing cholangitis (2022) · cites this paper as [51]
In the citing paper
“| 3 rd line | Naltrexone (12.5-50 mg/d) | Opioid withdrawal syndrome | 20,51 |”
From EASL Clinical Practice Guidelines on sclerosing cholangitis (2022) · cites this paper as [51]
In the citing paper
“In PBC, UDCA is used as first-line treatment,2 66 67 but 30%–50% of patients respond insufficiently (based on biochemical criteria)”
From Novel therapeutic targets for cholestatic and fatty liver disease (2022) · cites this paper as [66]
In the citing paper
“Current guideline-recommended medical treatment options for pruritus of cholestasis include the anion exchange resin cholestyramine, the pregnane X receptor (PXR) agonist rifampicin, the opioid antagonist naltrexone, and the selective serotonin reuptake inhibitor sertraline.4,7 Efficacy or tolerability of these drugs, or both, are limited.8,9”
From Fibrates for Itch (FITCH) in Fibrosing Cholangiopathies: A Double-Blind, Randomized, Placebo-Controlled Trial (2021) · cites this paper as [4]
In the citing paper
“Studies investigating the association between bone diseases and chronic liver disease have mainly focused on cholestatic liver diseases [20].”
From Bone diseases in patients with chronic liver disease (2019) · cites this paper as [20]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Transplant-assessment bilirubin threshold has conflicting units
MinorThe recommendation pairs a bilirubin threshold of 50 mmol/L with 3 mg/dl, while the transplantation discussion pairs a threshold of 50-85 lmol/L with 3-5 mg/dl. The two passages give incompatible units for the same approximate threshold.
“persistent elevated bilirubin values [50 mmol/L or 3 mg/dl]”
“bilirubin values are rising progressively above 50-85 lmol/L (3-5 mg/dl)”
LDL is described as both elevated and not elevated
MinorThe hyperlipidaemia section reports elevated LDL in early disease and says it may rise further, but later states that LDL cholesterol is not elevated.
“In early disease, elevated very low density lipoprotein (VLDL) and LDL concentrations are reported, as well as significantly elevated HDL values.As disease progresses, LDL may increase further”
“It is clinically significant that HDL cholesterol is elevated whilst LDL cholesterol is not”
Citations
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- Corpechot, 2016, Relationships between biochemical response to UDCA and progression of liver stiffness as determined by Fibroscan in patients with PBC, Hepatology, 64, 194A
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Metadata
- Authors
- Hirschfield, G. M., Beuers, U., Corpechot, C., Invernizzi, P., Jones, D., Marzioni, M., & Schramm, C.
- Affiliations
- European Association for the Study of the Liver (CH)
- ORCID
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2017-07
- Volume
- 67
- Issue
- 1
- Pages
- 145-172
- ISSN
- 0168-8278 (ISSN-L)
- OpenAlex
- W2605729742
- Semantic Scholar
- a6a2b9566f65a4e01153b95ecdcd0d4106d9fed9
- Cited by
- 1,480
- References
- 274
- Citations by year
- 2026: 166 · 2025: 207 · 2024: 205 · 2023: 178 · 2022: 175 · 2021: 140 · 2020: 136 · 2019: 131 · 2018: 111 · 2017: 30
- FWCI
- 68.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Hepatology (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by-nc-nd)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Funders
- European Association for the Study of the Liver
- DFG
- Helmut and Hannelore Greve Foundation
- YAEL-Foundation
- NIHR
- Birmingham Liver Biomedical Research Centre
- EU Marie Curie scheme
- Newcastle Biomedical Research Centre
- Medical Research Council
- Topics
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Health Sciences › Medicine › Rheumatology › IgG4-Related and Inflammatory Diseases
- Keywords
- primary biliary cirrhosis, autoimmune cholestatic liver disease, antimitochondrial antibodies, cholestatic hepatitis, risk stratification, ursodeoxycholic acid, obeticholic acid, fibrates, budesonide, off-label therapy, individualized care, diagnosis, management
- MeSH terms
- Cholangitis, Female, Humans, Male, Prognosis, Ursodeoxycholic Acid, Liver Transplantation, Practice Guidelines as Topic
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