Citations 23
Stratification of hepatocellular carcinoma risk in primary biliary cirrhosis: a multicentre international study
Lammers, Willem J. , Buuren, Henk R. van , Parés, Albert , Floreani, Annarosa , Janssen, Harry L.A. , Invernizzi, Pietro , Battezzati, Pier Maria , Ponsioen, Cyriel Y. , Poupon, Raoul , Mayo, Marlyn J. , Burroughs, Andrew K. , Nevens, Frederik , Lleò, Ana , Caballería, Llorenç , Lindor, Keith D. , Hirschfield, Gideon M. , Bruns, Tony , Boonstra, Kirsten , Trivedi, Palak Jitendrakumar , Corpechot, Christophe , Mason, Andrew L. , Kowdley, Kris V. , Hansen, Bettina E. , Bruns, Tony , Invernizzi, Pietro , Hirschfield, Gideon M
Gut | January 8, 2015 | Volume: 65 | Issue: 2 | Pages: 321-329
Objective Hepatocellular carcinoma (HCC) is an infrequent yet critical event in primary biliary cirrhosis (PBC); however, predictive tools remain ill-defined. Our objective was to identify candidate risk factors for HCC development in patients with PBC. Design Risk factor analysis was performed in over 15 centres from North America and Europe spanning >40 years observation period using Cox proportional hazards assumptions, logistic regression, and Kaplan-Meier estimates. Results Of 4565 patients with PBC 123 developed HCC, yielding an incidence rate (IR) of 3.4 cases/1000 patient-years. HCC was significantly more common in men (p<0.0001), and on univariate analysis factors at PBC diagnosis associated with future HCC development were male sex (unadjusted HR 2.91, p<0.0001), elevated serum aspartate transaminase (HR 1.24, p<0.0001), advanced disease (HR 2.72, p=0.022), thrombocytopenia (HR 1.65, p<0.0001), and hepatic decompensation (HR 9.89, p<0.0001). As such, non-treatment with ursodeoxycholic acid itself was not associated with cancer development; however, 12-month stratification by biochemical non-response (Paris-I criteria) associated significantly with future risk of HCC (HR 4.52, p<0.0001; IR 6.6 vs 1.4, p<0.0001). Non-response predicted future risk in patients with early stage disease (IR 4.7 vs 1.2, p=0.005), advanced disease (HR 2.79, p=0.02; IR 11.2 vs 4.4, p=0.033), and when restricting the analysis to only male patients (HR 4.44, p<0.001; IR 18.2 vs 5.4, p<0.001). On multivariable analysis biochemical non-response remained the most significant factor predictive of future HCC risk (adjusted HR 3.44, p<0.0001). Conclusions This uniquely powered, internationally representative cohort robustly demonstrates that 12-month biochemical non-response is associated with increased future risk of developing HCC in PBC. Such risk stratification is relevant to patient care and development of new therapies.
The IRF5–TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share
Kottyan, Leah C. , Zoller, Erin E., Bene, Jessica, Lu, Xiaoming , Kelly, Jennifer A. , Rupert, Andrew, Lessard, Christopher J. , Vaughn, Samuel , Marion, Miranda C. , Namjou, Bahram , Adler, Adam, Rasmussen, Astrid , Glenn, Stuart B., Montgomery, Courtney G. , Hirschfield, Gideon M. , Coltescu, Catalina, Amos, Chris, Ice, John A. , Registry, for UK Primary Sjögren's Syndrome, Rischmueller, Maureen , Brun, Johan G. , Gøransson, Lasse G. , Harboe, Erna, Omdal, Roald, Cunninghame‐Graham, Deborah S., Vyse, Tim J., Miceli‐Richard, Corinne , Lessard, James, Wahren‐Herlenius, Marie , Kvarnström, Marika , Illei, Gabor G. , Witte, Torsten, Jonsson, Roland , Nordmark, Gunnel , Ng, Wan‐Fai , Registry, for UK Primary Sjögren's Syndrome, Anaya, Juan‐Manuel , Rhodus, Nelson L., Segal, Barbara, Guthridge, Joel M. , Scofield, R. Hal , Alarcón‐Riquelme, Marta E. , Bae, Sang‐Cheol , Boackle, Susan A., Criswell, Lindsey A. , Gilkeson, Gary S. , Jacob, Chaim O., Kimberly, Robert P. , Brown, Elizabeth E. , Edberg, Jeffrey C., Alarcón, Graciela S. , Reveille, John D. , Vilá, Luis M. , Petri, Michelle , Niewold, Timothy B. , Stevens, Anne M., Tsao, Betty P. , Gorlova, Olga Y. , Wakeland, Ward, Radstake, Timothy R. D. J., Martín, Jose‐Ezequiel , Martı́n, Javier , Siminovitch, Katherine, Sivils, Kathy L., Gaffney, Patrick M. , Langefeld, Carl D. , Harley, John B., Kaufman, Kenneth M. , Niewold, Timothy, Weirauch, Matthew T. , Xie, Gang , Li, He , Nath, Swapan Kumar , Mariette, Xavier , Bowman, Simon , Registry, for UK Primary Sjögren's Syndrome, Lester, Sue , Brennan, Michael Thomas , Eriksson, Per , Registry, for UK Primary Sjögren's Syndrome, Merrill, Joan T. , James, Judith A. , Kamen, Diane L. , Ramsey‐Goldman, Rosalind , Freedman, Barry I. , Ying, Binwu , Mayes, Maureen D. , Hirschfield, Gideon M , Kottyan, Leah C , Guthridge, Joel M
Human Molecular Genetics | September 10, 2014 | Volume: 24 | Issue: 2 | Pages: 582-596
OC-030 Effective Stratification Of Hepatocellular Carcinoma Risk In Primary Biliary Cirrhosis: Results Of A Multi-centre International Study
Trivedi, PJ, Buuren, H. van, Battezzati, Pm, Floreani, Annarosa , Ponsioen, Cyriel Y. , Poupon, R., Mayo, Marlyn J. , Talwalkar, Jayant A., Burroughs, AK, Nevens, Frederik , Bruns, Tony , Li, KK, Cheung, Angela , Cazagon, N, Franceschet, I., Imam, Mohamad , Pieri, Giulia , Kanwar, Pushpjeet, Lindor, Keith D. , Lammers, Willem J. , Janssen, Harry L.A. , Invernizzi, Pietro , Parés, Albert , Corpechot, Christophe , Mason, Andrew L. , Kowdley, Kris V. , Kumagi, Teru , Lleò, Ana , Caballería, Llorenç , Boonstra, Kirsten , Vries, Esther de , Hansen, Bettina E. , Hirschfield, Gideon M. , Bruns, Tony
Gut | June 9, 2014 | Volume: 63 | Issue: Suppl 1 | Pages: A15-A16
Introduction Hepatocellular carcinoma (HCC) is an important but infrequent outcome in primary biliary cirrhosis (PBC). Improved risk evaluation is an important goal for stratified surveillance. Methods Risk-factor analysis of the ‘Global PBC Study Group’ comprising 15 centres across North America and Europe spanning >40-years follow-up was performed using Cox proportional hazards model, logistic regression and Kaplan-Meier estimates (SPSSv21). Results Of 3546 patients with PBC (med. follow-up 8.6 yrs; IQR 4.4–14.1), 131 developed HCC. Excluding those who developed HCC within 12 months of PBC diagnosis (n = 23), median time to HCC was 12.7 yrs (6.9–16.8) and subsequent survival 1.1 yrs. (0.2–2.7). At diagnosis, factors associated with HCC development were male gender (adj. HR: 4.4;1.4–12.2, p = 0.014) and thrombocytopenia (adj. HR: 4.5;1.4–14.8, p = 0.012). Use of ursodeoxycholic acid per-se was not associated with future risk of HCC, but stratification of risk by biochemical response at 12 months was effective by Rotterdam (adj. HR: 8.9;2.1–37.3, P = 0.003), Paris-I (adj. HR: 7.6;2.0–29.0, p = 0.003) or Toronto criteria (HR: 5.6;1.6–18.8, P = 0.006). Five (4.6 vs. 0.2%) and 10-year (13%vs.1.9%) HCC incidence was significantly increased for biochemical non-responders (p = 2.2 × 10 –9 ), and by multivariate analysis non-response remained the only significant risk factor. Conclusion Our uniquely powered cohort allows robust demonstration that 12-month biochemical non-response is associated with an increased risk of developing HCC in PBC. Routine surveillance in those achieving biochemical response is unlikely cost-effective. Disclosure of Interest None Declared.