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Cited by 924Liver Diseases and ImmunityPediatric Hepatobiliary Diseases and TreatmentsDrug Transport and Resistance Mechanisms

Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases

Open access
Lindor, Keith D., Bowlus, Christopher L., Boyer, James, Levy, Cynthia, Mayo, Marlyn·2019·Hepatology
DOI 10.1002/hep.30145
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Abstract

AASLD practice guidance on diagnostic and therapeutic care of PBC.

Integrity signals

Registry

Crossref · 10.1002/hep.30145

Cites

275 of 275 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

61 of 203 cited sources checked · 33 supported · 4 flagged · accuracy not yet measured

  • Premisecitation
    § CoNSeCUtiVe pBC/aiH

    The largest study found that only 8 of 1,476 patients with PBC later developed AIH.

    “while the largest study found that only 8 of 1,476 patients with PBC later developed AIH.(120)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [120] 120. Gossard AA, Lindor KD. Development of autoimmune hepa- titis in primary biliary cirrhosis. Liver Int. 2007;27:1086-1090. 121 source

      The Abstract and the ‘Frequency and Baseline Characteristics’ section report that 12 of 282 PBC patients developed AIH during follow-up, not 8 of 1,476. No page number is supplied for these passages in our copy. (LLM, conf=0.90)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Premisecitation
    § oCa

    In another phase 2 monotherapy study of 59 PBC patients, serum ALP dropped by 53.9% in the 10-mg OCA group, 37.2% in the 50-mg group, and 0.8% in the placebo group.

    “Serum ALP dropped by 53.9% in the 10-mg group, 37.2% in the 50-mg group, and by only 0.8% in the placebo group.(160)”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [160] 160. Kowdley KV, Luketic V, Chapman R, Hirschfield GM, Poupon R, Schramm C, et al. A randomized trial of obeti- cholic acid monotherapy in patients with primary biliary chol- angitis. Hepatology. 2018;67:1890-1902. 161 source

      The Trial Design section describes a phase 3 trial with placebo, 5–10-mg, and 10-mg groups, not a phase 2 study with a 50-mg group. The Secondary End Points section reports 12-month ALP reductions of 113, 130, and 14 U/L in those groups, respectively, rather than the claimed percentages. Page numbers were not available in our copy. (LLM, conf=0.88)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Premisecitation
    § oCa

    In a phase 2 randomized controlled trial of 165 patients, OCA at 10 mg, 25 mg, and 50 mg for 3 months achieved a 21% to 25% reduction in ALP compared with a 3% reduction with placebo.

    “A phase 2 randomized controlled trial evaluated 3 doses of OCA (10 mg, 25 mg, and 50 mg) against placebo for 3 months in a study including 165 patients.(159) A 21% to 25% reduction in ALP was achieved in the OCA groups compared with 3% reduction in the placebo group.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [159] 159. 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 ursode- oxycholic acid. Gastroenterology. 2015;148:751-761:e8. 160 source

      The Study Design and Abstract describe a three-month phase 2 randomized trial, but patients received 10 mg or 50 mg OCA—not 25 mg—and 59 patients were dosed, not 165. The Results (Primary Endpoint) report ALP reductions of 53.9% and 37.2% in the OCA groups versus 0.8% with placebo, contrary to the claimed 21%–25% versus 3%. Page numbers were not provided in our copy. (LLM, conf=0.94)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Premisecitation
    § Etiology of Primary Biliary Cholangitis

    PBC arises from a combination of genetic susceptibility and environmental triggers.

    “The etiology of PBC is thought to be due to a combination of genetic risk factors and environmental triggers.(5)(6)(7)”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [5] 5. Selmi C, Mayo MJ, Bach N, Ishibashi H, Invernizzi P, Gish G, et al. Primary biliary cirrhosis in monzygotic and dizygotic twins: Genetics, epigenetics, and environment. Gastroenterology. 2004;127:485-492. source
    • cites [6] 6. Shin S, Moh IH, Woo YS, Jung SW, Kim JB, Park JW, et al. Evidence from a familial case suggests maternal inher- itance of primary biliary cholangitis. World J Gastroenterol. 2017;23:7191-7197. source
    • cites [7] 7. Cheung AC, LaRusso NF, Gores GJ, Lazaridis KN. Epigenetics in the primary biliary cholangitis and primary sclerosing cholangitis. Semin Liver Dis. 2017;37:159-174. source
  • Premisecitation
    § asymptomatic Versus Symptomatic pBC

    A substantial proportion of asymptomatic PBC patients later develop symptoms, with 36% to 89% becoming symptomatic over average follow-up of 4.5 to 17.8 years.

    “All of these studies provide evidence of progressive disease in a substantial proportion of patients, with between 36% and 89% becoming symptomatic during average follow-up periods ranging from 4.5 to 17.8 years and a median time from diagnosis to the appearance of symptoms between 2 and 4.2 years.”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [44] 44. Long RG, Scheuer PJ, Sherlock S. Presentation and course of asymptomatic primary biliary cirrhosis. Gastroenterology. 1977;72:1204-1207. source
    • cites [45] 45. Mahl TC, Shockcor W, Boyer JL. Primary biliary cirrhosis: survival of a large cohort of symptomatic and asymptomatic patients followed for 24 years. J Hepatol. 1994;20:707-713. source
    • cites [46] 46. Mitchison HC, Lucey MR, Kelly PJ, Neuberger JM, Williams R, James OF. Symptom development and prognosis in primary biliary cirrhosis: a study in two centers. Gastroenterology. 1990;99:778-784. source

      The Abstract reports that 19 of 70 patients at Freeman Hospital and 15 of 25 at King's College Hospital developed symptoms—34 of 95 patients, or about 36%. The Results give a median follow-up of 69 months for initially asymptomatic patients. This study supports the lower symptom-development figure, but does not itself report 89% or average follow-up spanning 4.5 to 17.8 years; those figures in the citing sentence refer to the studies collectively. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • May combine two claims. 60
  • Classified as probably not a substantial claim. 16
  • The quote only partly states this claim. 1

  • May combine two claims.

    Premisecitation
    § oCa

    In that study, pruritus was the most important adverse event, leading to discontinuation of 38% of subjects in the 50-mg arm.

    “Again, pruritus was the most important adverse event, leading to discontinuation of 38% of study subjects in the 50-mg arm.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [160] 160. Kowdley KV, Luketic V, Chapman R, Hirschfield GM, Poupon R, Schramm C, et al. A randomized trial of obeti- cholic acid monotherapy in patients with primary biliary chol- angitis. Hepatology. 2018;67:1890-1902. 161 source

      The Safety and Side Effects section confirms that pruritus was the most common adverse event, but reports discontinuation due to pruritus in 10% of the 10-mg group and 1% of the 5–10-mg group. This trial had no 50-mg arm; the 38% figure is the incidence of pruritus in the placebo group, not a discontinuation rate. (LLM, conf=0.90)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation
    § aUtoaNtiBodieS

    Indirect immunofluorescence has the lowest sensitivity for AMA detection, with over 15% of AMA-negative sera by this method showing reactivity to MIT3.

    “The indirect immunofluorescence method has the lowest sensitivity, with over 15% of AMA-negative sera by indirect immunofluorescence showing reactivity to MIT3, a combination of three mitochondrial antigens.(87)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [87] 87. Bizzaro N, Covini G, Rosina F, Muratori P, Tonutti E, Villalta D, et al. Overcoming a "probable" diagnosis in antimitochon- drial antibody negative primary biliary cirrhosis: study of 100 sera and review of the literature. Clin Rev Allergy Immunol. 2012;42:288-297. source

      The indexed copy contains an IRIS repository listing and a PDF link, but no passage from the paper addressing assay sensitivity. Searches for MIT3, indirect immunofluorescence, and the claimed 15% figure found no relevant passage, so the claim cannot be checked against our copy. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation
    § SUrViVal prognostic Models

    The GLOBE score was developed from a retrospective cohort of 2,488 UDCA-treated patients and validated in 1,631 European and North American patients.

    “The GLOBE score was developed from a retrospective cohort of 2,488 UDCA-treated patients and validated by a second cohort of 1,631 European and North American patients.(74)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [74] 74. 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 pri- mary biliary cirrhosis receiving ursodeoxycholic acid therapy. Gastroenterology. 2015;149:1804-1812:e4. source

  • May combine two claims.

    Premisecitation
    § Etiology of Primary Biliary Cholangitis

    Genetic contribution to PBC is supported by higher monozygotic than dizygotic twin concordance and by HLA allele associations that vary by ethnicity.

    “In addition to the high concordance among monozygotic twins compared with dizygotic twins with PBC (5) , the strong association with human leukocyte antigen alleles, which vary by ethnicity, supports a genetic cause of inherited risk.(12)(13)(14)(15)(16)(17)(18)(19)(20)”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [5] 5. Selmi C, Mayo MJ, Bach N, Ishibashi H, Invernizzi P, Gish G, et al. Primary biliary cirrhosis in monzygotic and dizygotic twins: Genetics, epigenetics, and environment. Gastroenterology. 2004;127:485-492. source
    • cites [12] 12. Juran BD, Hirshfield GM, Invernizzi P, Atkinson EJ, Li Y, Xie G, et al. Immunochip analyses identify a novel risk locus for primary biliary cirrhosis at 13q1, multiple independent associ- ations at four established risk loci and epistasis between 1p31 and 7q32 risk variants. Hum Mol Genet. 2012;21:5209-5221. source
    • cites [13] 13. Johnson PJ, Qin S, Park JW, Poon RTP, Raoul JL, Philip PA, et al. Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: re- sults from the randomized phase III BRISK-FL study. J Clin Oncol. 2013;31:3517-3524. source

  • May combine two claims.

    Premisecitation
    § aMa-NegatiVe pBC

    Compared with AMA-positive PBC, AMA-negative PBC has higher prevalence of antinuclear and anti-smooth muscle antibodies and lower serum IgM levels.

    “Although AMA-negative PBC patients are nearly identical to AMA-positive PBC patients, minor differences have been noted, including a higher prevalence of antinuclear and anti-smooth muscle antibodies and lower serum IgM levels.(111)(112)(113)”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [111] 111. Lacerda MA, Ludwig J, Dickson ER, Jorgensen RA, Lindor KD. Antimitochondrial antibody-negative primary biliary cirrhosis. Am J Gastroenterol. 1995;90:247-249. 112 source
    • cites [112] 112. Michieletti P, Wanless IR, Katz A, Scheuer PJ, Yeaman SJ, Bassendine MF, et al. Antimitochondrial antibody negative primary biliary cirrhosis: a distinct syndrome of autoimmune cholangitis. Gut. 1994;35:260-265. 113 source
    • cites [113] 113. Invernizzi P, Crosignani A, Battezzati PM, Covini G, De Valle G, Larghi A, et al. Comparison of the clinical fea- tures and clinical course of antimitochondrial antibody-pos- itive and -negative primary biliary cirrhosis. Hepatology. 1997;25:1090-1095. 114 source

  • May combine two claims.

    Premisecitation
    § 4. In cases of suspected PBC/AIH overlap, treatment should be targeted at the predominant histological pattern of injury.

    A number of studies have shown benefit of UDCA in PBC, with individual studies demonstrating consistent evidence of improved liver biochemistries.

    “A number of studies have shown the benefit of UDCA in this context.(58)(59)(60)(61)(62)(63) Individual studies have demonstrated consistent evidence of improved liver biochemistries.”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [58] 58. Heathcote EJ, Cauch-Dudek K, Walker V, Bailey RJ, Blendis LM, Ghent CN, et al. The Canadian Multicenter Double- blind Randomized Controlled Trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology. 1994;19:1149-1156. source
      Experimental — accuracy not yet measured
    • cites [59] 59. Lindor KD, Therneau TM, Jorgensen RA, Malinchoc M, Dickson ER. Effects of ursodeoxycholic acid on survival in patients with primary biliary cirrhosis. Gastroenterology. 1996;110:1515-1518. source
      Experimental — accuracy not yet measured
    • cites [60] 60. Pares A, Caballeria L, Rodes J. Excellent long-term survival in patients with primary biliary cirrhosis and biochemical response to ursodeoxycholic Acid. Gastroenterology. 2006;130:715-720. source

  • May combine two claims.

    Premisecitation
    § Fatigue

    Fatigue is the most common symptom in PBC, found in 50% to 78% of patients, and has a significant negative impact on quality of life.

    “Fatigue is the most common symptom in PBC; it has been found in 50% to 78% of patients and has a significant negative impact on quality of life.(95)(96)”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [95] 95. Newton JLJD. Modafinil is effective treatment for excessive daytime somnolence and fatigue in primary biliary cirrhosis [Abstract]. Hepatology. 2006;44:628A. source

      The Associations Between NHP Scores and the Characteristics of PBC section reports a significant association between fatigue and worse overall quality of life. The Discussion says fatigue was the finding most often associated with quality-of-life subscores, not that it was the most common symptom; it gives a prevalence range of 8%–80% across prior studies, not 50%–78%. Page numbers are unavailable in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [96] 96. Poupon RE, Chretien Y, Chazouilleres O, Poupon R, Chwalow J. Quality of life in patients with primary biliary cir- rhosis. Hepatology. 2004;40:489-494. source

      The Associations Between NHP Scores and the Characteristics of PBC section reports a significant association between fatigue and worse overall quality of life. The Discussion calls fatigue the finding most often associated with quality-of-life scores, not the most common symptom, and reports prevalence across prior studies as 8%–80%, not 50%–78%. Page numbers are unavailable in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § oVerlap oF aiH WitH pBC

    PBC/AIH overlap syndrome may also refer to patients with PBC followed sequentially by AIH or, less commonly, AIH followed by PBC.

    “A PBC/AIH overlap syndrome may also refer to patients with PBC followed sequentially by AIH or, less commonly, AIH followed by PBC.(119)(120)(121)”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [119] 119. Efe C, Ozaslan E, Heurgue-Berlot A, Kav T, Masi C, Purnak T, et al. Sequential presentation of primary biliary cirrho- sis and autoimmune hepatitis. Eur J Gastroenterol Hepatol. 2014;26:532-537. 120 source
    • cites [120] 120. Gossard AA, Lindor KD. Development of autoimmune hepa- titis in primary biliary cirrhosis. Liver Int. 2007;27:1086-1090. 121 source
    • cites [121] 121. Poupon R, Chazouilleres O, Corpechot C, Chretien Y. Development of autoimmune hepatitis in patients with typical primary biliary cirrhosis. Hepatology. 2006;44:85-90. 122 source

  • May combine two claims.

    Premisecitation
    § MaNageMeNt oF SyMptoMS

    The symptoms of PBC significantly impair quality of life and do not typically improve with UDCA or OCA treatment.

    “The symptoms of PBC significantly impair quality of life (182) and do not typically improve with UDCA or OCA treatment.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [182] 182. Mells GF, Pells G, Newton JL, Bathgate AJ, Burroughs AK, Heneghan MA, et al. Impact of primary biliary cirrho- sis on perceived quality of life: the UK-PBC national study. Hepatology. 2013;58:273-283. 183 source

  • May combine two claims.

    Premisecitation
    § other drugs

    Doubling the dose of UDCA and adding colchicine, methotrexate, or silymarin have not been found to be of benefit over and beyond that achieved with UDCA alone.

    “Doubling the dose of UDCA and adding colchicine, methotrexate, or silymarin have not been found to be of benefit over and beyond that achieved with UDCA alone.(163,178,179)”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [163] 163. Kaplan MM, Cheng S, Price LL, Bonis PA. A randomized controlled trial of colchicine plus ursodiol versus methotrex- ate plus ursodiol in primary biliary cirrhosis: ten-year results. Hepatology. 2004;39:915-923. 164

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [178] 178. Angulo P, Patel T, Jorgensen RA, Therneau TM, Lindor KD. Silymarin in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid. Hepatology. 2000;32:897-900. 179 source
    • cites [179] 179. Angulo P, Jorgensen RA, Lindor KD. Incomplete response to ursodeoxycholic acid in primary biliary cirrhosis: is a double dosage worthwhile? Am J Gastroenterol. 2001;96:3152-3157. 180 source

      The Discussion (page not specified) says adding colchicine showed no benefit for patients with a suboptimal response to UDCA. It also reports negative results from larger controlled trials of methotrexate, while acknowledging biochemical improvement in a few selected patients. Our copy does not establish the claimed lack of benefit from doubling the UDCA dose or adding silymarin. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation
    § 4. In cases of suspected PBC/AIH overlap, treatment should be targeted at the predominant histological pattern of injury.

    Patients with earlier histologic stage usually respond more favorably to UDCA than patients with advanced disease, although patients with advanced disease may benefit in survival or avoid liver transplantation with this therapy.

    “However, patients with earlier histologic stage usually respond more favorably to UDCA than patients with advanced disease, although patients with advanced disease may benefit in survival or avoid liver transplantation with this therapy.(63)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [63] 63. Poupon RE, Lindor KD, Cauch-Dudek K, Dickson ER, Poupon R, Heathcote EJ. Combined analysis of randomized controlled trials of ursodeoxycholic acid in primary biliary cir- rhosis. Gastroenterology. 1997;113:884-890. source

      The Discussion suggests UDCA might be less efficacious when introduced later in disease, but does not establish that earlier histologic stages usually respond more favorably. For the outcome this study measured, survival free of transplantation, the subgroup analysis found a significant benefit at stage IV but not at stages I–II or III (Figure 3, Discussion). The claim that patients with advanced disease may benefit is supported. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation
    § Arranged by year Response criteria

    Pruritus was the most common adverse event in the phase 3 trial but was less common in patients undergoing dose titration starting at 5 mg/day.

    “As with the phase 2 studies, pruritus was the most common adverse event, but it was less common in patients undergoing dose titration starting at 5 mg/day.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [161] 161. Nevens F, Andreone P, Mazzella G, Strasser SI, Bowlus C, Invernizzi P, et al. A placebo-controlled trial of obeti- cholic acid in primary biliary cholangitis. N Engl J Med. 2016;375:631-643. 162 source

  • May combine two claims.

    Premisecitation
    § Arranged by year Response criteria

    In a phase 3 trial of 210 patients treated for 1 year, the primary endpoint was met by 46% in the titration group, 47% in the 10 mg/day group, and 10% in the placebo group.

    “After 1 year, this primary endpoint was met by 46% of patients in the titration group, 47% in the 10 mg/day group, and 10% of patients in the placebo group.(161)”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [161] 161. Nevens F, Andreone P, Mazzella G, Strasser SI, Bowlus C, Invernizzi P, et al. A placebo-controlled trial of obeti- cholic acid in primary biliary cholangitis. N Engl J Med. 2016;375:631-643. 162 source

  • May combine two claims.

    Premisecitation
    § 4. In cases of suspected PBC/AIH overlap, treatment should be targeted at the predominant histological pattern of injury.

    UDCA therapy does not improve fatigue, pruritus, associated bone disease, or autoimmune features found in association with PBC.

    “However, UDCA therapy does not improve fatigue, pruritus, associated bone disease, or autoimmune features found in association with PBC.(69,89,153,154)”
    Quote in the paperNot a substantial claim1 of 4 sources checked
    • cites [69] 69. Lindor KD, Jorgensen RA, Therneau TM, Malinchoc M, Dickson ER. Ursodeoxycholic acid delays the onset of esoph- ageal varices in primary biliary cirrhosis. Mayo Clin Proc. 1997;72:1137-1140. source
    • cites [89] 89. Degott C, Zafrani ES, Callard P, Balkau B, Poupon RE, Poupon R. Histopathological study of primary biliary cirrhosis and the effect of ursodeoxycholic acid treatment on histology progression. Hepatology. 1999;29:1007-1012. source

      The paper’s ‘Effect of UDCA Therapy on Histological Progression’ and ‘UDCA Therapy and Histology Progression’ sections assess liver-biopsy findings, not whether UDCA improves fatigue, pruritus, bone disease, or associated autoimmune features. Searches for those symptoms and conditions found no passage addressing the claimed lack of improvement; page numbers were not supplied for the passages. (LLM, conf=0.75)

      Experimental — accuracy not yet measured
    • cites [153] 153. Balan V, Dickson ER, Jorgensen RA, Lindor KD. Effect of ursodeoxycholic acid on serum lipids of patients with primary biliary cirrhosis. Mayo Clin Proc. 1994;69:923-929. 154 source
    • cites [154] 154. Lindor KD, Janes CH, Crippin JS, Jorgensen RA, Dickson ER. Bone disease in primary biliary cirrhosis: Does ursodeoxy- cholic acid make a difference? Hepatology. 1995;21:389-392. 155

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation
    § rifampicin

    Drug-induced liver injuries, sometimes progressing to acute liver failure, hemolysis, renal impairment, and alteration in drug metabolism, have been reported with rifampicin use, so use is avoided in patients with bilirubin levels greater than 2.5 mg/dL.

    “Although uncommon, drug-induced liver injuries-sometimes progressing to acute liver failure, hemolysis, renal impairment, and alteration in drug metabolism-have all been reported with rifampicin use such that use is avoided in patients with bilirubin levels greater than 2.5 mg/dL, with close follow-up warranted.(195,199)”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [195] 195. Bachs L, Pares A, Elena M, Piera C, Rodes J. Comparison of rifampicin with phenobarbitone for treatment of pruritus in biliary cirrhosis. Lancet. 1989;1:574-576. 196 source
    • cites [199] 199. Prince MI, Burt AD, Jones DE. Hepatitis and liver dysfunc- tion with rifampicin therapy for pruritus in primary biliary cirrhosis. Gut. 2002;50:436-439. 200 source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • The quote only partly states this claim.

    Premisecitation
    § oSteopeNia/oSteoporoSiS

    Etidronate does not improve outcomes compared with placebo in osteoporotic patients.

    “Etidronate was ineffective compared with placebo”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [239] 239. Guanabens N, Monegal A, Cerda D, Muxi A, Gifre L, Peris P, et al. Randomized trial comparing monthly ibandronate and weekly alendronate for osteoporosis in patients with pri- mary biliary cirrhosis. Hepatology. 2013;58:2070-2078. 240 source

      The introduction mentions trials of etidronate in patients with primary biliary cirrhosis, including bisphosphonate comparisons with placebo, but gives no result for etidronate versus placebo. The Results report outcomes for ibandronate and alendronate only. Searches for etidronate’s effectiveness versus placebo found no passage establishing the claimed lack of benefit. (LLM, conf=0.74)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation
    § Selective Serotonin reuptake inhibitors

    Although the itch in cholestasis does not appear to be histamine-related, antihistamines may be beneficial in patients with cholestasis, probably because of their sedative properties.

    “Although the itch in cholestasis does not appear to be histamine-related, antihistamines may be beneficial in patients with cholestasis, probably because of their sedative properties.(214,215)”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [214] 214. Rishe E, Azarm A, Bergasa NV. Itch in primary bili- ary cirrhosis: a patients' perspective. Acta Derm Venereol. 2008;88:34-37. 215) source

      The indexed Abstract (page unavailable) reports that patients with primary biliary cirrhosis most commonly associated antihistamines with itch relief. It does not establish that cholestatic itch is unrelated to histamine or attribute the reported relief to antihistamines’ sedative properties. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [215] 215. Greaves MW. Antihistamines in dermatology. Skin Pharmacol Physiol. 2005;18:220-229. 216

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationcitation
    § loNg-terM FolloW-Up

    Periodic monitoring of liver tests helps detect patients who are inadequate responders to UDCA after 12 months of therapy, lack of adherence, and the rare patients who go on to develop AIH.

    “This helps detect patients who are inadequate responders to UDCA after 12 months of therapy, lack of adherence, and the rare patients who go on to develop AIH.(121,135,224,225)”
    Quote in the paperSubstantial claim1 of 4 sources checked
    • cites [121] 121. Poupon R, Chazouilleres O, Corpechot C, Chretien Y. Development of autoimmune hepatitis in patients with typical primary biliary cirrhosis. Hepatology. 2006;44:85-90. 122 source
    • cites [135] 135. Chazouilleres O, Wendum D, Serfaty L, Rosmorduc O, Poupon R. Long term outcome and response to therapy of primary biliary cirrhosis-autoimmune hepatitis overlap syn- drome. J Hepatol. 2006;44:400-406. 136 source
    • cites [224] 224. Colombato LA, Alvarez F, Cote J, Huet PM. Autoimmune cholangiopathy: the result of consecutive primary bili- ary cirrhosis and autoimmune hepatitis? Gastroenterology. 1994;107:1839-1843. 225 source
    • cites [225] 225. Weyman RL, Voigt M. Consecutive occurrence of primary biliary cirrhosis and autoimmune hepatitis: a case report and review of the literature. Am J Gastroenterol. 2001;96:585-587. 226 source

  • May combine two claims.

    Premisecitation
    § liVer traNSplaNtatioN

    Ibandronate and alendronate have similar efficacy and safety.

    “both drugs have a comparable efficacy and safety profile.(239)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [239] 239. Guanabens N, Monegal A, Cerda D, Muxi A, Gifre L, Peris P, et al. Randomized trial comparing monthly ibandronate and weekly alendronate for osteoporosis in patients with pri- mary biliary cirrhosis. Hepatology. 2013;58:2070-2078. 240 source

  • May combine two claims.

    Premisecitation
    § liVer traNSplaNtatioN

    Recurrent PBC develops in 20%-30% of transplant recipients by 10 years and up to 50% by 20 years.

    “Some 20% to 30% of patients with PBC who undergo transplantation develop recurrent disease over 10 years, and up to 50% do so by 20 years of follow-up.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [256] 256. Duclos-Vallee JC, Sebagh M. Recurrence of autoimmune dis- ease, primary sclerosing cholangitis, primary biliary cirrhosis, and autoimmune hepatitis after liver transplantation. Liver Transpl. 2009;15(Suppl 2):S25-S34. 257 source
    • cites [257] 257. Bosch A, Dumortier J, Maucort-Boulch D, Scoazec JY, Wendum D, Conti F, et al. Preventive administration of UDCA after liver transplantation for primary biliary cirrhosis is associated with a lower risk of disease recurrence. J Hepatol. 2015;63:1449-1458. 258 source

      The Recurrence Rate section reports recurrent PBC in 17% of patients using strict histologic criteria; Table 4 gives an estimate of 26% using expanded criteria. Neither is a 10-year estimate: the Patient Groups section reports mean follow-up of 4.7 years and a maximum of 13.8 years. The paper does not support the claim of up to 50% recurrence by 20 years. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation
    § NatUral HiStory iN tHe UdCa era (CirCa 1990)

    Randomized trials, combined analyses, and long-term observational studies show UDCA improves biochemical indices, delays histologic progression, and improves survival without transplantation.

    “Several randomized trials, combined analyses, and long-term observational studies have shown that UDCA not only improves biochemical indices but also delays histologic progression and improves survival without transplantation.(53,(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [53] 53. Corpechot C, Carrat F, Bonnand AM, Poupon RE, Poupon R. The effect of ursodeoxycholic acid therapy on liver fibro- sis progression in primary biliary cirrhosis. Hepatology. 2000;32:1196-1199. source
    • cites [56] 56. Angulo P, Batts KP, Therneau TM, Jorgensen RA, Dickson ER, Lindor KD. Long-term ursodeoxycholic acid delays histo- logical progression in primary biliary cirrhosis. Hepatology. 1999;29:644-647.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [57] 57. Combes B, Carithers RL Jr, Maddrey WC, Lin D, McDonald MF, Wheeler DE, et al. A randomized, double-blind, place- bo-controlled trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology. 1995;22:759-66. source

  • May combine two claims.

    Premisecitation
    § other predictions of prognosis

    Bilirubin level is the best predictor of survival and the most important component in all mathematical prognostic models in PBC.

    “The bilirubin level is the best predictor of survival and is the most important component in all mathematical models of prognosis in PBC.(71,76)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [71] 71. Dickson ER, Grambsch PM, Fleming TR, Fisher LD, Langworthy A. Prognosis in primary biliary cirrhosis: model for decision making. Hepatology. 1989;10:1-7. source
    • cites [76] 76. Grambsch PM, Dickson ER, Kaplan M, LeSage G, Fleming TR, Langworthy AL. Extramural cross-validation of the Mayo primary biliary cirrhosis survival model establishes its generalizability. Hepatology. 1989;10:846-850. source

  • May combine two claims.

    Premisecitation
    § SUrViVal prognostic Models

    The UK-PBC score involved 3,165 patients and found that serum ALP, aminotransferases, and bilirubin after 12 months of therapy, plus baseline albumin and platelets, predicted risk of liver transplant or liver-related death within 5, 10, or 15 years.

    “The UK-PBC score involved a cohort of 3,165 patients and found that serum ALP, amino transferases, and bilirubin after 12 months of therapy-as well as albumin and platelets at baseline-predicted the risk of a liver transplant or liver-related death occurring within 5, 10, or 15 years.(75)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [75] 75. 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 cholangitis. Hepatology. 2016;63:930-950.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation
    § aMa-NegatiVe pBC

    AMA-negative PBC patients have more nonhepatic autoimmune conditions and worse health-related quality of life in social and emotional domains than AMA-positive patients.

    “Compared with AMA-positive PBC patients, AMAnegative PBC patients have more nonhepatic autoimmune conditions (114)(115) and worse health-related quality of life in social and emotional domains.(116)”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [114] 114. Sakauchi F, Mori M, Zeniya M, Toda G. Antimitochondrial antibody negative primary biliary cirrhosis in Japan: utiliza- tion of clinical data when patients applied to receive public financial aid. J Epidemiol. 2006;16:30-34. 115 source
    • cites [115] 115. Juliusson G, Imam M, Bjornsson ES, A. TJ, Lindor KD. Long- term outcomes in antimitochondrial antibody negatve primary biliary cirrhosis. Scand J Gastroenterol. 2016;51:745-752. 116 source
    • cites [116] 116. Raszeja-Wyszomirska J, Wunsch E, Krawczyk M, Rigopoulou EI, Kostrzewa K, Norman GL, et al. Assessment of health related quality of life in polish patients with primary biliary cirrhosis. Clin Res Hepatol Gastroenterol. 2016;40:471-479. 117 source

  • May combine two claims.

    Premisecitation
    § diagNoSiS oF pBC/aiH oVerlap

    Paris criteria have been met in 1% to 14.2% of PBC patients, with higher rates found in Hispanic PBC patients.

    “These criteria have been met in 1% to 14.2% of PBC patients, with higher rates found in Hispanic PBC patients.(128)(129)(130)(131)(132)(133)”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [128] 128. Lohse AW, zum Buschenfelde KH, Franz B, Kanzler S, Gerken G, Dienes HP. Characterization of the overlap syndrome of primary biliary cirrhosis (PBC) and autoimmune hepatitis: evidence for it being a hepatitic form of PBC in genetically susceptible individuals. Hepatology. 1999;29:1078-1084. 129 source
    • cites [129] 129. Joshi S, Cauch-Dudek K, Wanless IR, Lindor KD, Jorgensen R, Batts K, et al. Primary biliary cirrhosis with additional fea- tures of autoimmune hepatitis: response to therapy with ur- sodeoxycholic acid. Hepatology. 2002;35:409-413. 130 source
    • cites [130] 130. Heurgue A, Vitry F, Diebold MD, Yaziji N, Bernard-Chabert B, Pennaforte JL, et al. Overlap syndrome of primary biliary cirrhosis and autoimmune hepatitis: a retrospective study of 115 cases of autoimmune liver disease. Gastroenterol Clin Biol. 2007;31:17-25. 131 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § 4. In cases of suspected PBC/AIH overlap, treatment should be targeted at the predominant histological pattern of injury.

    The proposed mechanisms of action of UDCA include choleretic, cytoprotective, anti-inflammatory, and immunomodulatory properties.

    “The proposed mechanisms of action of UDCA are multiple and include choleretic, cytoprotective, anti-inflammatory, and immunomodulatory properties.(141)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [141] 141. Paumgartner G, Beuers U. Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revis- ited. Hepatology. 2002;36:525-531. 142 source

  • May combine two claims.

    Premisereasoning
    § diagNoSiS oF pBC/aiH oVerlap

    The International Autoimmune Hepatitis Group score was designed to diagnose AIH by excluding other liver diseases including PBC, so it gives positive points for absence of non-PBC factors and negative points for AMA and biliary features.

    “However, the International Autoimmune Hepatitis Group score was designed for the diagnosis of AIH with the exclusion of other liver diseases, including PBC, and therefore positive points are given for the absence of factors unrelated to a diagnosis of PBCe.g., viral hepatitis and alcohol abuse-and negative scores are given for AMA and/or biochemical/histologic features of biliary disease.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisereasoning
    § CoNSeCUtiVe pBC/aiH

    These patients may no longer have AMA seropositivity, and their liver histology becomes more typical of AIH that responds to immunosuppressive therapy.

    “These patients may no longer have AMA seropositivity, and liver histology becomes more typical of AIH that responds to immunosuppressive therapy.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § 4. In cases of suspected PBC/AIH overlap, treatment should be targeted at the predominant histological pattern of injury.

    UDCA is widely used and has demonstrated the ability to reduce the need for liver transplantation for PBC.

    “UDCA is widely used and has demonstrated the ability to produce a reduction in need for liver transplantation for PBC.(144)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [144] 144. Lee J, Belanger A, Doucette JT, Stanca C, Friedman S, Bach N. Transplantation trends in primary biliary cirrhosis. Clin Gastroenterol Hepatol. 2007;5:1313-1315. 145 source

  • May combine two claims.

    Premisecitation
    § aMa-NegatiVe pBC

    Treatment response to UDCA appears similar in AMA-negative and AMA-positive PBC, and whether clinical outcome differences exist is unresolved.

    “However, treatment response to UDCA appears similar in AMA-negative and AMA-positive PBC patients, and whether there are differences in clinical outcomes has not been resolved.(113,115)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [113] 113. Invernizzi P, Crosignani A, Battezzati PM, Covini G, De Valle G, Larghi A, et al. Comparison of the clinical fea- tures and clinical course of antimitochondrial antibody-pos- itive and -negative primary biliary cirrhosis. Hepatology. 1997;25:1090-1095. 114 source
    • cites [115] 115. Juliusson G, Imam M, Bjornsson ES, A. TJ, Lindor KD. Long- term outcomes in antimitochondrial antibody negatve primary biliary cirrhosis. Scand J Gastroenterol. 2016;51:745-752. 116 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given
    § diagNoSiS oF pBC/aiH oVerlap

    The wide variability among studies of PBC/AIH overlap may be due to genetic and environmental factors and to nonuniform collection of biochemical, serological, immunological, and histological data.

    “The wide variability among studies may be due to a variety of genetic and environmental factors as well as the nonuniform collection of biochemical, serological, immunological, and histological data.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § CliNiCal CoUrSe oF oVerlap SyNdroMe

    In that study, an estimated 50% of patients in either group had received UDCA, and some in both groups had received a variety of other therapies.

    “However, an estimated 50% of patients in either group had received treatment with UDCA, and some in both groups had received a variety of other therapies.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [134] 134. Silveira MG, Talwalkar JA, Angulo P, Lindor KD. Overlap of autoimmune hepatitis and primary biliary cirrhosis: long-term outcomes. Am J Gastroenterol. 2007;102:1244-1250. 135 source

  • May combine two claims.

    Premisecitation
    § 4. In cases of suspected PBC/AIH overlap, treatment should be targeted at the predominant histological pattern of injury.

    Some meta-analyses have questioned the results of UDCA studies, often including short-duration studies and studies using what is now known to be an inadequate dose of UDCA.

    “Some meta-analyses have questioned these results.(142) Often, these meta-analyses include studies of short duration and those that have used what is now known to be an inadequate dose of UDCA.(143)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [142] 142. Goulis J, Leandro G, Burroughs AK. Randomised controlled trials of ursodeoxycholic-acid therapy for primary biliary cir- rhosis: a meta-analysis. Lancet. 1999;354:1053-1060. 143 source
    • cites [143] 143. Gong Y, Huang Z, Christensen E, Gluud C. Ursodeoxycholic acid for patients with primary biliary cirrhosis: an updated systematic review and meta-analysis of randomized clinical trials using Bayesian approach as sensitivity analyses. Am J Gastroenterol. 2007;102:1799-1807. 144 source

  • May combine two claims.

    Premisecitation
    § Fatigue

    Early studies reported pruritus in 20% to 70% of PBC patients; it is now less common because more patients are diagnosed in the early asymptomatic phase.

    “Early studies reported that pruritus (itching) occurs in 20% to 70% of patients with PBC.It is now less common because of the growing number of patients with PBC who are diagnosed in the early, asymptomatic phase.(100)(101)(102)”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [100] 100. Prince MI, Chetwynd A, Craig WL, Metcalf JV, James OF. Asymptomatic primary biliary cirrhosis: clinical features, prognosis, and symptom progression in a large population based cohort. Gut. 2004;53:865-870. 101 source
    • cites [101] 101. Talwalkar JA, Souto E, Jorgensen RA, Lindor KD. Natural history of pruritus in primary biliary cirrhosis. Clin Gastroenterol Hepatol. 2003;1:297-302. 102 source
    • cites [102] 102. Pares A, Rodes J. Natural history of primary biliary cirrhosis. Clin Liver Dis. 2003;7:779-794. 103 source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § abdominal pain

    Right upper quadrant pain is found in approximately 17% of PBC patients; it is typically nonspecific, not progressive, not well correlated with disease stage or hepatomegaly, and often disappears spontaneously; its etiology is unknown.

    “Right upper quadrant pain is found in approximately 17% of patients with PBC.It is typically nonspecific in character, not progressive in nature, not well correlated with disease stage or hepatomegaly, and often disappears spontaneously.Its etiology is unknown.(108)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [108] 108. Laurin JM, DeSotel CK, Jorgensen RA, Dickson ER, Lindor KD. The natural history of abdominal pain asso- ciated with primary biliary cirrhosis. Am J Gastroenterol. 1994;89:1840-1843. 109

  • May combine two claims.

    Premisecitation
    § diagNoSiS oF pBC/aiH oVerlap

    When the revised International Autoimmune Hepatitis Group score was applied to PBC cohorts, fewer than 1% of PBC patients met definite AIH criteria and 8% to 19% met probable AIH criteria.

    “This score was subsequently revised (122) and, when applied to PBC cohorts, revealed that less than 1% of PBC patients met definite AIH diagnostic criteria, while 8% to 19% met probable AIH criteria.(123)(124)”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [122] 122. Alvarez F, Berg PA, Bianchi FB, Bianchi L, Burroughs AK, Cancado EL, et al. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. 1999;31:929-938. 123 source
    • cites [123] 123. Talwalkar JA, Keach JC, Angulo P, Lindor KD. Overlap of auto- immue hepatitis and primary biliary cirrhosis: an evaluation of a modified scoring system. Am J Gastroenterol. 2002;97:1191-1197. 124 source
    • cites [124] 124. Suzuki Y, Arase Y, Ikeda K, Saitoh S, Tsubota A, Suzuki F, et al. Clinical and pathological characteristics of the auto- immune hepatitis and primary biliary cirrhosis overlap syn- drome. J Gastroenterol Hepatol. 2004;19:699-706. 125 source

  • May combine two claims.

    Interpretationcitation
    § CliNiCal CoUrSe oF oVerlap SyNdroMe

    UDCA with or without immunosuppressive therapy has been used for PBC/AIH overlap, but no clear consensus on optimal therapy for these patients exists.

    “UDCA with or without immunosuppressive therapy has been used, but no clear consensus on optimal therapy for these patients exists.(129)(130)(134)(135)”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [129] 129. Joshi S, Cauch-Dudek K, Wanless IR, Lindor KD, Jorgensen R, Batts K, et al. Primary biliary cirrhosis with additional fea- tures of autoimmune hepatitis: response to therapy with ur- sodeoxycholic acid. Hepatology. 2002;35:409-413. 130 source
    • cites [130] 130. Heurgue A, Vitry F, Diebold MD, Yaziji N, Bernard-Chabert B, Pennaforte JL, et al. Overlap syndrome of primary biliary cirrhosis and autoimmune hepatitis: a retrospective study of 115 cases of autoimmune liver disease. Gastroenterol Clin Biol. 2007;31:17-25. 131 source
    • cites [134] 134. Silveira MG, Talwalkar JA, Angulo P, Lindor KD. Overlap of autoimmune hepatitis and primary biliary cirrhosis: long-term outcomes. Am J Gastroenterol. 2007;102:1244-1250. 135 source

  • May combine two claims.

    Premisecitation
    § other drugs

    Budesonide may be helpful in PBC, although this is controversial.

    “Budesonide may be helpful, although this is controversial.(180)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [180] 180. Angulo P, Jorgensen RA, Keach JC, Dickson ER, Smith C, Lindor KD. Oral budesonide in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ur- sodeoxycholic acid. Hepatology. 2000;31:318-323. 181

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § 4. In cases of suspected PBC/AIH overlap, treatment should be targeted at the predominant histological pattern of injury.

    A 5-pound weight gain over the first year of UDCA therapy has been reported and is not progressive.

    “A 5-pound weight gain over the first year of therapy has been reported and is not progressive.(155)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [155] 155. Siegel JL, Jorgensen R, Angulo P, Lindor KD. Treatment with ur- sodeoxycholic acid is associated with weight gain in patients with primary biliary cirrhosis. J Clin Gastroenterol. 2003;37:183-185. 156 source

  • May combine two claims.

    Premisecitation
    § MaNageMeNt oF FatigUe

    Altered serotonin neurotransmission may mediate fatigue in chronic liver disease, but ondansetron did not relieve fatigue in a clinical trial.

    “Altered serotonin neurotransmission may mediate fatigue in chronic liver disease (183) ; however, ondansetron, an antagonist to serotonin receptor, did not relieve fatigue in a clinical trial.(184)”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [183] 183. Jones EA. Relief from profound fatigue associated with chronic liver disease by long-term ondansetron therapy. Lancet. 1999;354:397. 184

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [184] 184. Theal JJ, Toosi MN, Girlan L, Heslegrave RJ, Huet PM, Burak KW, et al. A randomized, controlled crossover trial of ondansetron in patients with primary biliary cirrhosis and fa- tigue. Hepatology. 2005;41:1305-1312. 185 source

  • May combine two claims.

    Premisecitation
    § MaNageMeNt oF FatigUe

    Modafinil was originally reported to lessen fatigue in PBC in open-label studies, but a subsequent placebo-controlled trial failed to show benefit.

    “Modafinil, a stimulant used for narcolepsy, was originally reported to lessen fatigue in PBC in open-label studies.(186,187) However, a subsequent placebo-controlled trial failed to show benefit.(188)”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [186] 186. Kaplan MM, Bonis PA. Modafinil for the treatment of fatigue in primary biliary cirrhosis. Ann Intern Med. 2005;143:546-547. 187 source
    • cites [187] 187. Jones DE, Newton JL. An open study of modafinil for the treatment of daytime somnolence and fatigue in primary bili- ary cirrhosis. Aliment Pharmacol Ther. 2007;25:471-476. 188 source
    • cites [188] 188. Silveira MG, Gossard AA, Stahler AC, Jorgensen RA, Petz JL, Ali AH, et al. A randomized, placebo-controlled clini- cal trial of efficacy and safety: modafinil in the treatment of fatigue in patients with primary biliary cirrhosis. Am J Ther. 2017;24:e167-e76. 189 source

  • May combine two claims.

    Premisenone given
    § proMiSiNg NeW drUgS Fibrates

    Fibrates can cause elevation of transaminases, which is also typically reversible.

    “Finally, fibrates can cause elevation of transaminases, which is also typically reversible.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given
    § 4. In cases of suspected PBC/AIH overlap, treatment should be targeted at the predominant histological pattern of injury.

    Improvement in liver tests is typically observed within a few weeks, and 90% of the improvement usually occurs within 6 to 9 months.

    “Improvement in liver tests are typically observed within a few weeks, and 90% of the improvement usually occurs within 6 to 9 months.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § 4. In cases of suspected PBC/AIH overlap, treatment should be targeted at the predominant histological pattern of injury.

    UDCA use has been associated with a reduction of serum low-density lipoprotein cholesterol levels, a reduced risk of developing varices, and slower histologic progression.

    “The use of UDCA has been associated with a reduction of serum low-density lipoprotein cholesterol levels, a reduced risk of developing varices, and slower histologic progression.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § proMiSiNg NeW drUgS Fibrates

    The serum creatinine elevation with fibrates is typically reversible, not associated with a decline in glomerular filtration rate, and attributed to an increase in creatinine production.

    “This is typically reversible and not associated with a decline in glomerular filtration rate, but it is attributed to an increase in creatinine production.(167)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [167] 167. Davidson MH, Armani A, McKenney JM, Jacobson TA. Safety considerations with fibrate therapy. Am J Cardiol. 2007;99:3C-18C. 168 source

  • May combine two claims.

    Premisecitation
    § proMiSiNg NeW drUgS Fibrates

    In that trial, improvement in pruritus and beneficial effects on markers of fibrosis were also observed.

    “Furthermore, improvement in pruritus and beneficial effects on markers of fibrosis were also observed.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [94] 94. Corpechot C, Chazouillères O, Rousseau A, Guyader D, Habersetzer F, Mathurin P, et al. A 2-year multicenter, double-blind, randomized, placebo-controlled study of be- zafibrate for the treatment of primary biliary cholangitis in patients with inadequate biochemical response to ursodeoxy- cholic acid therapy (Bezurso). J Hepatol. 2017;66:S89. source

  • May combine two claims.

    Premisecitation
    § oCa

    OCA is a farnesoid X receptor agonist that is 100 times more potent than the endogenous ligand chenodeoxycholic acid.

    “OCA is a farnesoid X receptor (FXR) agonist that is 100 times more potent than the endogenous ligand, chenodeoxycholic acid.(156)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [156] 156. Pellicciari R, Fiorucci S, Camaioni E, Clerici C, Costantino G, Maloney PR, et al. 6α-ethyl-chenodeoxycholic acid (6- ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity. J Med Chem. 2002;45:3569-3572. 157 source

  • May combine two claims.

    Premisecitation
    § proMiSiNg NeW drUgS Fibrates

    Use of fibrates can be associated with myalgias and heartburn, and an elevation in serum creatinine is frequently observed.

    “Notably, use of fibrates can be associated with myalgias and heartburn, and an elevation in serum creatinine is frequently observed.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § proMiSiNg NeW drUgS Fibrates

    Older patients and those with lower fibrosis scores were more likely to respond to bezafibrate.

    “Older patients and those with lower fibrosis scores were more likely to respond.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [166] 166. Reig A, Sese P, Pares A. Effects of bezafibrate on outcome and pruritus in primary biliary cholangitis with subopti- mal ursodeoxycholic acid response. Am J Gastroenterol. 2018;113:49-55. 167 source

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given
    § dry Mouth (Xerostomia)

    Comorbidities such as excessive alcohol consumption, obesity, and cigarette smoking promote liver disease progression and may put the individual at risk of not being accepted for a liver transplant.

    “These comorbidities both promote disease progression and may put the individual at risk of not being accepted for a liver transplant should the latter become necessary.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given
    § HorMoNe replaCeMeNt aNd pregNaNCy

    Estrogens promote cholestasis, so oral contraceptive pills and estrogen supplements may induce or worsen pruritus.

    “Estrogens promote cholestasis, so oral contraceptive pills and estrogen supplements may induce or worsen pruritus.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § MaNageMeNt oF FatigUe

    Intractable fatigue is not a valid indication for liver transplantation because fatigue usually persists post transplant.

    “Intractable fatigue is not a valid indication for liver transplantation because fatigue usually persists post transplant.(189)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [189] 189. Carbone M, Bufton S, Monaco A, Griffiths L, Jones DE, Neuberger JM. The effect of liver transplantation on fatigue in patients with primary biliary cirrhosis: a prospective study. J Hepatol. 2013;59:490-494. 190 source

  • Classified as probably not a substantial claim.

    Interpretationreasoning
    § MaNageMeNt oF FatigUe

    At this time, there is no recommended therapy for fatigue resulting from PBC.

    “At this time, there is no recommended therapy for the fatigue resulting from PBC.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning
    § HorMoNe replaCeMeNt aNd pregNaNCy

    A short second stage of labor is optimal because the Valsalva maneuver may precipitate variceal hemorrhage.

    “A short second stage of labor is optimal because the Valsalva maneuver may precipitate variceal hemorrhage.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § anion-exchange resins

    It is not known which substance in the gut the anion-exchange resins bind to improve cholestatic itching, and clinical trials proving their efficacy are limited, but they have a long track record of clinical use.

    “It is not known which substance in the gut they may be binding to that leads to improved cholestatic itching, and clinical trials proving their efficacy are limited, but they have a long track record of clinical use.(190,191)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [190] 190. Datta DV, Sherlock S. Cholestyramine for long term re- lief of the pruritus complicating intrahepatic cholestasis. Gastroenterology. 1966;50:323-332. 191 source
    • cites [191] 191. Van Itallie TB, Hashim SA, Crampton RS, Tennent DM. The treatment of pruritus and hypercholesteremia of pri- mary biliary cirrhosis with cholestyramine. N Engl J Med. 1961;265:469-474. 192 source

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given
    § HorMoNe replaCeMeNt aNd pregNaNCy

    There are limited data about fertility or infant outcome in PBC patients.

    “There are limited data about fertility or infant outcome in PBC patients.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given
    § dry Mouth (Xerostomia)

    The majority of individuals currently have no symptoms referable to their liver disease when diagnosed with PBC.

    “The majority of individuals currently have no symptoms referable to their liver disease when diagnosed with PBC.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning
    § dry Mouth (Xerostomia)

    Lack of symptoms makes it particularly difficult for an individual with PBC to recognize the importance of preventive strategies.

    “This lack of symptoms makes it particularly difficult for an individual to recognize the importance of preventive strategies in PBC.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § anion-exchange resins

    Colesevalam was not effective in a single placebo-controlled trial of cholestatic pruritus, although only patients who had already failed other resins were enrolled.

    “Colesevalam was not effective in a single placebo-controlled trial of cholestatic pruritus.(192) However, only patients who had already failed other resins were enrolled.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [192] 192. Kuiper EM, van Erpecum KJ, Beuers U, Hansen BE, Thio HB, de Man RA, et al. The potent bile acid sequestrant cole- sevelam is not effective in cholestatic pruritus: results of a dou- ble-blind, randomized, placebo-controlled trial. Hepatology. 2010;52:1334-1340. 193 source

  • May combine two claims.

    Premisecitation
    § Selective Serotonin reuptake inhibitors

    Sertraline at a dose of 75 to 100 mg helped relieve pruritus in a single small placebo-controlled trial and in a retrospective case series, with the effect independent from improvement in depression.

    “Sertraline, given at a dose of 75 to 100 mg, helped relieve pruritus in a single, small, placebo-controlled trial and in a retrospective case series.The effect was independent from an improvement in depression.(209)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [209] 209. Mayo MJ, Handem I, Saldana S, Jacobe H, Getachew Y, Rush AJ. Sertraline as a first-line treatment for cholestatic pruritus. Hepatology. 2007;45:666-674. 210 source

  • May combine two claims.

    Premisecitation
    § Selective Serotonin reuptake inhibitors

    Phenobarbital can improve cholestatic pruritus but is a strong sedative that worsens or initiates fatigue, increases vitamin D deficiency, and has been associated with troublesome gingival hyperplasia.

    “Phenobarbital can improve cholestatic pruritus but is a strong sedative that worsens or initiates fatigue, increases vitamin D deficiency, and has been associated with troublesome gingival hyperplasia.(213)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [213] 213. Bloomer JR, Boyer JL. Phenobartial effectis in cholestatic liver disease. Ann Intern Med. 1975;82:310-317. 214 source

  • May combine two claims.

    Premisecitation
    § MaNageMeNt oF portal HyperteNSioN

    Portal hypertension in PBC can arise from biliary cirrhosis or, before cirrhosis, from nodular regenerative hyperplasia.

    “Patients with PBC may develop portal hypertension as a result of biliary cirrhosis or, in the precirrhotic stage of the disease, in association with nodular regenerative hyperplasia.(232,233)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [232] 232. Kew MC, Varma RR, Santos HAD, Scheuer PJ. Portal hyper- tension in primary biliary cirrhosis. Gut. 1971;12:830-834. 233

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [233] 233. Abraham SC, Kamath PS, Eghtesad B, Demetris AJ, Krasinskas AM. Liver transplantation in precirrhotic bili- ary tract disease: Portal hypertension is frequently associated with nodular regenerative hyperplasia and obliterative portal venopathy. Am J Surg Pathol. 2006;30:1454-1461. 234 source

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisereasoning
    § HorMoNe replaCeMeNt aNd pregNaNCy

    During pregnancy in PBC, itching may become severe even early on and may fail to resolve completely after delivery.

    “Similarly, during pregnancy, itching may become severe even early on in the pregnancy, and it may fail to resolve completely after delivery in patients with PBC.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § Selective Serotonin reuptake inhibitors

    Ondansetron was initially reported to decrease cholestatic itch but was later found to be no better than placebo in more rigorous trials.

    “Ondansetron, a serotonin antagonist, was initially reported to decrease cholestatic itch but was later found to be no better than placebo in more rigorous trials.(210)(211)(212)”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [210] 210. Raderer M, Muller C, Scheithauer W. Ondansetron for pruri- tus due to cholestasis. N Engl J Med. 1994;330:1540. 211 source
    • cites [211] 211. Schworer H, Ramadori G. Improvement of cholestatic pruri- tus by ondansetron. Lancet. 1993;341:1277. 212 source
    • cites [212] 212. Jones EA, Molenaar HA, Oosting J. Ondansetron and pruritus in chronic liver disease: a controlled study. Hepatogastroenterology. 2007;54:1196-1199. 213

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given
    § dry Mouth (Xerostomia)

    Patients with dry mouth are at increased risk of dental caries.

    “Patients with dry mouth are at increased risk of dental caries and should receive regular professional dental cleanings and check-ups.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given
    § HorMoNe replaCeMeNt aNd pregNaNCy

    Treatment with beta blockers is safe in pregnancy.

    “Treatment with beta blockers is safe in pregnancy.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation
    § HyperlipideMia

    A meta-analysis found a pooled cardiovascular risk of 1.57 (95% CI, 1.21-2.06) in PBC patients with hypercholesterolemia.

    “This has been challenged by a meta-analysis that identified a pooled risk of 1.57 (95% CI, 1.21-2.06)(247)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [247] 247. Ungprasert P, Wijarnpreecha K, Ahuja W, Spanuchart I, Thongprayoon C. Coronary artery disease in primary biliary cirrhosis: A systematic review and meta-analysis of observa- tional studies. Hepatol Res. 2015;45:1055-1061. 248 source

  • May combine two claims.

    Premisecitation
    § liVer traNSplaNtatioN

    Cyclosporine-based long-term immunosuppression may reduce recurrent PBC incidence, though this is unproven.

    “Long-term immunosuppression with a cyclosporine-based regimen seems to be associated with reduced incidence of recurrent PBC, but this is not proven.(259)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [259] 259. Charatcharoenwitthaya P, Pimentel S, Talwalkar JA, Enders FT, Lindor KD, Krom RA, et al. Long-term survival and im- pact of ursodeoxycholic acid treatment for recurrent primary biliary cirrhosis after liver transplantation. Liver Transpl. 2007;13:1236-1245. 260 source

  • May combine two claims.

    Premisecitation
    § liVer traNSplaNtatioN

    After transplantation, osteopenia can worsen for 6 months, but bone density returns to baseline by 12 months and then improves.

    “Osteopenia may worsen for the first 6 months after transplantation, but bone mineral density returns to baseline after 12 months and improves thereafter.(254)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [254] 254. Eastell R, Dickson ER, Hodgson SF, Wiesner RH, Porayko MK, Wahner HW, et al. Rates of vertebral bone loss before and after liver transplantation in women with primary biliary cirrhosis. Hepatology. 1991;14:296-300. 255 source

  • May combine two claims.

    Premisecitation
    § liVer traNSplaNtatioN

    Fatigue improves in some PBC patients after transplantation, but moderate-to-severe fatigue still affects about half at 2 years.

    “Fatigue improves in a subset of patients with PBC, but moderate to severe fatigue continues to affect nearly half of patients 2 years after liver transplantation.(189)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [189] 189. Carbone M, Bufton S, Monaco A, Griffiths L, Jones DE, Neuberger JM. The effect of liver transplantation on fatigue in patients with primary biliary cirrhosis: a prospective study. J Hepatol. 2013;59:490-494. 190 source

  • May combine two claims.

    Premisecitation
    § liVer traNSplaNtatioN

    That study reported 1-, 3-, 5-, and 10-year graft survival of 85%, 80%, 78.1%, and 71.9%, and patient survival of 90.2%, 86.7%, 84.4%, and 79%.

    “In the same study, the 1-, 3-, 5-, and 10-year graft survival rates were 85%, 80%, 78.1%, and 71.9%, and the 1-, 3-, 5-, and 10-year patient survival rates were 90.2%, 86.7%, 84.4%, and 79%, respectively.(253)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [253] 253. Singal AK, Guturu P, Hmoud B, Kuo YF, Salameh H, Wiesner RH. Evolving frequency and outcomes of liver trans- plantation based on etiology of liver disease. Transplantation. 2013;95:755-760. 254 source

  • May combine two claims.

    Premisecitation
    § oSteopeNia/oSteoporoSiS

    Hormone replacement therapy improves bone mineral density somewhat in PBC, but safety concerns limit its use.

    “Hormone replacement therapy has led to some improvement in bone mineral density, but these agents are seldom used because of safety concerns.(243)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [243] 243. Boone RH, Cheung AM, Girlan LM, Heathcote EJ. Osteoporosis in primary biliary cirrhosis: a randomized trial of the efficacy and feasibility of estrogen/progestin. Dig Dis Sci. 2006;51:1103-1112. 244 source
72 of 72

  • The paper relies on this without support.

    Accepted treatments for sicca syndrome work equally well in patients with PBC even though they have not been studied specifically in that population.

    “Although not studied specifically in patients with PBC, accepted treatments for sicca syndrome appear to work equally well in this population.”

  • The paper relies on this without support.

    OCA was approved by the Food and Drug Administration in May 2016 for use with UDCA in PBC patients with inadequate response to at least 1 year of UDCA or as monotherapy for UDCA-intolerant patients.

    “OCA was approved by the Food and Drug Administration in May 2016 to be used in combination with UDCA in patients with PBC who have inadequate response to at least 1 year of treatment with UDCA, or as monotherapy for those patients who are intolerant to UDCA.”

  • The paper relies on this without support.

    Men and those with advanced disease are most likely to develop hepatocellular cancer.

    “Men and patients with advanced disease are most apt to develop hepatocellular cancer”

  • The paper relies on this without support.

    Hepatocellular cancer occurs at 3.9 cases per 1,000 person-years in PBC.

    “which was found at a rate of 3.9 cases in 1,000 per year of follow-up.”

  • The paper relies on this without support.

    Fat-soluble vitamin deficiency is uncommon in most PBC patients.

    “Most PBC patients do not develop fat-soluble vitamin (vitamins A, D, E, and K) deficiency.”

  • The paper relies on this without support.

    Chronic fatigue is not a transplant indication since it does not always reverse after liver transplantation.

    “Chronic fatigue is not an indication for transplant because this symptom is not universally reversible after liver transplantation.”

  • The paper relies on this without support.

    Severe, intractable pruritus is an uncommon indication for liver transplantation.

    “Severe intractable pruritus is an exceptional indication for liver transplantation.”

  • The paper relies on this without support.

    Liver transplantation indications for PBC resemble those for other chronic liver diseases.

    “Indications for liver transplantation for patients with PBC are similar to those with other forms of chronic liver disease.”

  • The paper relies on this without support.

    Platelet counts can guide the need for endoscopic surveillance.

    “Platelet counts can be used to determine the need for endoscopic surveillance.”

  • The paper relies on this without support.

    UDCA lowers LDL cholesterol and is the first-line step.

    “UDCA will lower low-density lipoprotein cholesterol levels and is the initial step.”
10 of 10

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?

  • Currently, fibrates are only approved by the FDA as lipid-lowering medications in the United States and multiple countries rather than PBC treatment.

    “Currently, fibrates are only approved by the FDA as lipid-lowering medications in the United States (US) and multiple countries rather than PBC treatment [7].”

    From Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor (2025) · cites this paper as [7]

    The “Promising New Drugs—Fibrates” section says fibrates are approved by the FDA only as lipid-lowering medications, and the Guidance section calls their use for PBC off-label. These passages support the US approval claim but do not establish their approval status in multiple other countries; page numbers were not supplied. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The AASLD notes that fibrates, including fenofibrate, may improve pruritus in PBC, based on observational studies and clinical experience, but most high-quality randomized controlled trial data specifically address bezafibrate rather than fenofibrate.

    “The AASLD notes that fibrates, including fenofibrate, may improve pruritus in PBC, based on observational studies and clinical experience, but most high-quality randomized controlled trial data specifically address bezafibrate rather than fenofibrate [7].”

    From Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor (2025) · cites this paper as [7]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • The AASLD notes that fenofibrate can cause transient elevations in transaminases, but not associated with any toxicity and normalize with therapy discontinuation.

    “The AASLD notes that fenofibrate can cause transient elevations in transaminases, but not associated with any toxicity and normalize with therapy discontinuation [7].”

    From Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor (2025) · cites this paper as [7]

    The “Promising New Drugs—Fibrates” section (page unavailable) says fibrates can elevate transaminases and that the elevation is typically reversible; it also discusses fenofibrate as a fibrate. But it says hepatotoxicity remains a concern and that the elevation may not represent hepatotoxicity—not that it is unassociated with any toxicity. It does not specifically say levels normalize after treatment discontinuation. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Fibrates modulate hepatic stellate cell activation; regulate bile acid synthesis and detoxification, and phospholipid secretion.

    “The fibrates modulate hepatic stellate cell activation; as it regulates bile acid synthesis and detoxification, and phospholipid secretion [7,38].”

    From Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor (2025) · cites this paper as [7]

    The “Promising New Drugs—Fibrates” section says fibrates activate PPAR and that PPAR-α regulates bile acid synthesis and detoxification and phospholipid secretion. It also mentions antifibrotic properties of PPAR-δ and PPAR-γ activation, but does not say that fibrates modulate hepatic stellate cell activation. Page numbers are unavailable in our copy. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • These effects collectively reduce cholesterol and hepatic inflammation, reflected by reductions in serum ALP and GGT levels.

    “These effects collectively reduce cholesterol and hepatic inflammation, and it reflects by reductions in serum ALP and GGT levels [7,15,39].”

    From Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor (2025) · cites this paper as [7]

    In “Therapy for PBC” (page unavailable), the guidance describes anti-inflammatory properties of UDCA, improved liver biochemistries, and reduced LDL cholesterol; it specifically uses serum ALP to monitor treatment response. It does not report a reduction in GGT or establish that changes in ALP and GGT reflect reduced hepatic inflammation. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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.

  • Conflicting liver-stiffness thresholds for variceal surveillance

    Major

    The follow-up text gives a transient-elastography threshold of at least 7 kPa for upper endoscopy, while Table 2 and the portal-hypertension discussion give 17 kPa. The different thresholds could change who is referred for surveillance.

  • Alendronate comparison cites an unrelated reference

    Minor

    The sentence cites reference 255 for a comparison of alendronate and etidronate, but reference 255 is about lipoproteins rather than either drug.

  • Four conditions follow a claim of three

    Minor

    The sentence says there are three major autoimmune diseases but lists four: Sjögren syndrome, CREST, scleroderma, and Raynaud disease.

3 of 3

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. 2016, Screening of antimitochondrial antibody subtype M2 in residents at least 18 years of age in an urban district of Shanghai, China. Eur Rev Med Pharmacol Sci, 20, 2052
  2. 2005, Practice Guidelines Committee AAftSoLD, Management of hepatocellular carcinoma. Hepatology, 42, 1208

Cited by

Sorted by citations

Related

Authors
Lindor, K. D., Bowlus, C. L., Boyer, J., Levy, C., & Mayo, M.
Affiliations
  • Mayo Clinic (US)
  • University of California, Davis (US)
  • Yale University (US)
  • University of Miami (US)
  • The University of Texas Southwestern Medical Center (US)
Corresponding author
Lindor, Keith D.
ORCID
Venue
Hepatology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2018-11-06
Volume
69
Issue
1
Pages
394-419
ISSN
  • 0270-9139 (ISSN-L)
  • 1527-3350
DOI
10.1002/hep.30145
OpenAlex
W2886703787
Cited by
913
References
263
Citations by year
2026: 126 · 2025: 147 · 2024: 143 · 2023: 131 · 2022: 114 · 2021: 113 · 2020: 81 · 2019: 55 · 2018: 2 · 2017: 1
FWCI
39.24
Type
journal article
Language
en
Open access
Licence
Locations
  • Hepatology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Bristol-Myers Squibb
  • Eli Lilly and Company
  • GlaxoSmithKline
  • American Association for the Study of Liver Diseases
  • Gilead Sciences
  • Allergan
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, obeticholic acid, antimitochondrial antibodies, autoimmune etiology, diagnosis, imaging, clinical features, treatment, screening, cholestasis, liver fibrosis, biliary strictures, cholangitis
MeSH terms
Humans, Liver Cirrhosis, Biliary

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-09-28.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-09-28.

Cited sources are checked by gpt-6-sol.

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.

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