Cholangiocarcinoma is associated with a raised enhanced liver fibrosis score independent of primary sclerosing cholangitis

Saffioti, Francesca; Roccarina, Davide; Vesterhus, Mette; Hov, Johannes R.; Rosenberg, William; Pinzani, Massimo; Pereira, Stephen P.; Boberg, Kirsten Muri; Thorburn, Douglas

doi:10.1111/eci.13088

Cited by 13 publications

(15 citation statements)

References 42 publications

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“…Forty studies that collectively included 16 094 subjects were evaluated, of which 26 studies of non‐invasive prognostic markers that included 13 759 subjects with PSC were included in the systematic review (Figure 1). Five studies focused on ALP value 6‐10 (Table 1), eight studies evaluated models that included tests obtained from blood with or without clinical variables 11‐18 (Table 2), six studies evaluated elastography or scores derived from MRI findings 19‐24 (Table 3) and seven studies evaluated novel biomarkers 25‐31 (Table 4). The most common primary outcomes assessed were a composite clinical outcome that included one or more of the following outcomes: survival, transplant‐free survival, hepatic decompensation or cholangiocarcinoma (N = 12 studies), followed by transplant‐free survival, liver transplant or death (N = 10 studies).…”

Section: Resultsmentioning

confidence: 99%

“…Weismuller et al was the largest study (N = 7121), included the largest number of patients with small duct PSC (N = 254) and PSC‐AIH variant (N = 470) and compared outcomes to those with classical PSC (N = 6397). Two studies included subjects diagnosed before 18 years old 15,18 …”

Section: Resultsmentioning

confidence: 99%

“…The Amsterdam‐Oxford model, which includes subtypes of PSC (large or small duct), as well as age, and blood tests, predicts liver‐related death and liver transplant with modest accuracy and should be compared to other prognostic models 13 . The ELF score is associated with increased liver stiffness on VCTE and higher scores are seen in patients with cholangiocarcinoma 15 . A potential limitation of the ELF score is it is a proprietary score associated with additional costs compared to other scores where clinical or laboratory information are readily available.…”

Section: Discussionmentioning

confidence: 99%

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Systematic review: non‐invasive prognostic tests for primary sclerosing cholangitis

Mazhar

Russo

2021

Aliment Pharmacol Ther

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SummaryBackgroundSeveral prognostic tests for primary sclerosing cholangitis (PSC) have been developed, including biochemical models, elastography and magnetic resonance imaging scores.AimTo conduct a systematic review of non‐invasive prognostic tests for PSC.MethodsA systematic review was conducted from 1987 to 2020 of blood tests, biochemical models, elastography and imaging scores associated with outcomes in PSC.ResultsForty studies of prognostic tests that collectively included 16 094 subjects with PSC were reviewed, of which 26 studies of non‐invasive tests including 13 759 subjects with PSC were included. Normalisation or reduction of alkaline phosphatase with or without therapy was associated with transplant‐free survival and reduced risk of hepatobiliary cancers but cut‐off values for alkaline phosphatase were not consistent among studies. The most studied prognostic biochemical model was the Mayo Risk Score (MRS) evaluated in 18 studies with a c‐statistic from 0.63 to 0.85 for clinical outcomes. One study demonstrated that the UK‐PSC score outperforms MRS for predicting clinical outcomes with a c‐statistics of 0.81and 0.75 respectively. A transient elastography score greater than 11.1 kPa is associated with survival and liver‐related complications. The Anali score, derived from specific MRI and MRCP features, is associated with the development of cholangiocarcinoma and decompensated cirrhosis. Promising prognostic models include the enhanced liver fibrosis (ELF) score, ELF test and PREsTo scores.ConclusionMRS is the most studied prognostic score for clinical outcomes in PSC but the UK‐PSC score and PREsTo have better test performance. Further studies comparing MRS to UK‐PSC score, PREsTo or ELF with elastography or imaging‐based scores are warranted.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Systematic review: non‐invasive prognostic tests for primary sclerosing cholangitis

Mazhar

Russo

2021

Aliment Pharmacol Ther

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“…A retrospective study examined ELF scores in 32 patients with PSC and cholangiocarcinoma (CCA), 36 patients with CCA, and 119 patients with PSC alone [ 11 ]. ELF scores were significantly higher in CCA without chronic liver disease and in PSC + CCA compared to PSC alone ( p < 0.001).…”

Section: Resultsmentioning

confidence: 99%

“…By multivariate analysis, MRS (OR 8.14), CCA (OR 5.36), and older age (OR 1.07) were associated with an elevated ELF score. An optimal cutoff ELF score of 10.1 was associated with a c-statistic of 0.74, a sensitivity of 81%, and a specificity of 60% [ 11 ].…”

Section: Resultsmentioning

confidence: 99%

Systematic Review of Prognostic Models Compared to the Mayo Risk Score for Primary Sclerosing Cholangitis

Schmeltzer

Russo

2021

JCM

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Background: Primary sclerosing cholangitis (PSC) is a cholestatic liver disease with a variable clinical course that can ultimately lead to end-stage liver disease, cholangiocarcinoma, and the need for liver transplantation. Several prognostic models have been developed to predict clinical outcomes and have been compared to the revised Mayo Risk Score (rMRS). Aim: To conduct a systematic review comparing the rMRS to other non-invasive prognostic tests for PSC. Methods: A systematic review of studies from 2000 to 2020 was performed that compared non-invasive biochemical prognostic models to the rMRS in predicting outcomes in patients with PSC. Results: Thirty-seven studies were identified, of which five studies that collectively included 3230 patients were reviewed. Outcomes included transplant-free survival or composite clinical outcomes. The rMRS was better than the Amsterdam–Oxford model for predicting 1-year transplant-free survival, c-statistics 0.75 and 0.70, respectively. The UK-PSC score outperformed the rMRS for 10-year transplant-free survival, c-statistics 0.85 and 0.69, respectively. An enhanced liver fibrosis score was independently associated with transplant-free survival after adjusting for rMRS. PREsTo predicts 5-year hepatic decompensation with a c-statistic modestly higher than rMRS; 0.90 and 0.85, respectively. Conclusion: Newer prognostic models, including the UK-PSC score and PREsTo, are more accurate at predicting clinical endpoints in PSC compared to the rMRS. Time frames and clinical endpoints are not standard among studies.

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Blood‐based tumor fibrosis markers as diagnostic and prognostic biomarkers in patients with biliary tract cancer

Christensen

Jensen

Larsen

et al. 2022

Intl Journal of Cancer

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Biliary tract cancer (BTC) is characterized by a desmoplastic extracellular matrix (ECM). We tested the diagnostic and prognostic use of seven circulating biomarkers of ECM remodeling: pro‐peptides of type III collagen (PRO‐C3), VI (PRO‐C6) and XI (PRO‐C11), matrix metalloprotease (MMP) degraded type III collagen (C3M) and type IV collagen (C4M) fragments, granzyme B degraded type IV collagen fragments (C4G) and MMP degraded and citrullinated vimentin (VICM) a marker of macrophage activation. The study included 269 patients with all stages of BTC and 49 patients with benign biliary tract diseases. Serum samples from BTC patients were collected before surgery, or before first‐ or second‐line chemotherapy. C3M, C4M, PRO‐C3, PRO‐C6, PRO‐C11 and VICM levels were elevated in patients with BTC compared to patients with benign disease. Receiver operating characteristics curve analyses identified PRO‐C3 (area under curve [AUC] = 0.87) as the ECM marker with the best diagnostic performance. The ECM biomarkers correlated with inflammation biomarkers (C‐reactive protein [CRP], interleukin‐6 [IL‐6] and YKL‐40) but not with CA19‐9. To investigate prognostic performance, patients were split into three cohorts (first‐line, second‐line and surgery). Elevated ECM biomarker levels were associated with short overall survival (OS), but only pretreatment PRO‐C3 and PRO‐C6 were associated with OS in both the first‐line and second‐line settings when adjusting for CA19‐9, performance status and stage in a multivariate Cox‐regression analyses. Our results indicate that collagen remodeling is increased in patients with BTC and associated with survival. The collagen pro‐peptides (PRO‐C3 and PRO‐C6) could be used as novel biomarkers in these patients.

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Cholangiocarcinoma is associated with a raised enhanced liver fibrosis score independent of primary sclerosing cholangitis

Cited by 13 publications

References 42 publications

Systematic review: non‐invasive prognostic tests for primary sclerosing cholangitis

Systematic review: non‐invasive prognostic tests for primary sclerosing cholangitis

Systematic Review of Prognostic Models Compared to the Mayo Risk Score for Primary Sclerosing Cholangitis

Blood‐based tumor fibrosis markers as diagnostic and prognostic biomarkers in patients with biliary tract cancer

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