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      Prognostic indicators in hepatocellular carcinoma: a systematic review of 72 studies

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          Abstract

          Background

          Although there are many studies of the predictors of death in hepatocellular carcinoma (HCC), most combine patients with and without cirrhosis and many combine those with compensated and decompensated cirrhosis.

          Objective

          To perform a systematic review of the literature evaluating the predictors of death in patients with cirrhosis and HCC and to evaluate whether the predictors differ between patients with compensated and decompensated cirrhosis.

          Methods

          Inclusion criteria: (i) publication in English, (ii) adult patients, (c) >80% of the patients had cirrhosis, (iv) follow-up >6 months and (v) multivariable analysis. Quality was based on the accepted quality criteria for prognostic studies.

          Results

          Of the 1106 references obtained, 947 were excluded because they did not meet the inclusion criteria. A total of 23 968 patients were included in 72 studies (median, 177/study); 77% male, median age 64, 55% Child–Pugh class A. The most robust predictors of death were portal vein thrombosis, tumour size, α-foetoprotein and Child–Pugh class. Sensitivity analysis using only 15 ‘good’ studies and 22 studies in which all patients had cirrhosis yielded the same variables. In the studies including mostly compensated or decompensated patients, the predictors were both liver and tumour related. However, these studies were few and the results were not robust.

          Conclusions

          This systematic review of 72 studies shows that the most robust predictors of death in patients with cirrhosis and HCC are tumour related and liver related. Future prognostic studies should include these predictors and should be performed in specific patient populations to determine whether specific prognostic indicators are more relevant at different stages of cirrhosis.

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          Most cited references77

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          Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver.

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            Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials.

            This study analyzed the natural history and prognostic factors of patients with nonsurgical hepatocellular carcinoma (HCC). Twenty variables from 102 cirrhotic patients with HCC who were not treated within prospective randomized controlled trials (RCT) were investigated through uni- and multivariate analyses. None of them was suitable for radical therapies (surgical resection, liver transplantation, or ethanol injection) or presented end-stage disease as reflected by an Okuda stage 3 or a Performance Status >/=3. Sixty-five patients were Child-Pugh A, 34 were B, and 3 were C. Most of them exhibited a preserved Performance Status Test (PST) (0 = 56; 1 = 38; 2 = 8). Tumor was solitary in 26 (
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              Assessing the generalizability of prognostic information.

              Physicians are often asked to make prognostic assessments but often worry that their assessments will prove inaccurate. Prognostic systems were developed to enhance the accuracy of such assessments. This paper describes an approach for evaluating prognostic systems based on the accuracy (calibration and discrimination) and generalizability (reproducibility and transportability) of the system's predictions. Reproducibility is the ability to produce accurate predictions among patients not included in the development of the system but from the same population. Transportability is the ability to produce accurate predictions among patients drawn from a different but plausibly related population. On the basis of the observation that the generalizability of a prognostic system is commonly limited to a single historical period, geographic location, methodologic approach, disease spectrum, or follow-up interval, we describe a working hierarchy of the cumulative generalizability of prognostic systems. This approach is illustrated in a structured review of the Dukes and Jass staging systems for colon and rectal cancer and applied to a young man with colon cancer. Because it treats the development of the system as a "black box" and evaluates only the performance of the predictions, the approach can be applied to any system that generates predicted probabilities. Although the Dukes and Jass staging systems are discrete, the approach can also be applied to systems that generate continuous predictions and, with some modification, to systems that predict over multiple time periods. Like any scientific hypothesis, the generalizability of a prognostic system is established by being tested and being found accurate across increasingly diverse settings. The more numerous and diverse the settings in which the system is tested and found accurate, the more likely it will generalize to an untested setting.
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                Author and article information

                Journal
                Liver Int
                liv
                Liver International
                Blackwell Publishing Ltd
                1478-3223
                1478-3231
                April 2009
                : 29
                : 4
                : 502-510
                Affiliations
                [1 ]simpleDigestive Diseases Section, Yale University School of Medicine New Haven, CT, USA
                [2 ]simpleVA Connecticut Healthcare System West Haven, CT, USA
                [3 ]simpleDivision of Gastroenterology, University of Alberta Edmonton, AB, Canada
                Author notes
                Correspondence Guadalupe Garcia-Tsao, Professor of Medicine, 333 Cedar Street-1080 LMP, New Haven, CT 06520, USA Tel: +203 737 6063 Fax: +203 785 7273 e-mail: guadalupe.garcia-tsao@ 123456yale.edu
                Article
                10.1111/j.1478-3231.2008.01957.x
                2711257
                19141028
                85b20ecf-2cd2-4ab1-bd7c-a0dc12a8ab64
                © 2009 John Wiley & Sons A/S

                Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

                History
                : 28 August 2008
                : 29 October 2008
                Categories
                Clinical Studies

                Gastroenterology & Hepatology
                prognosis,multivariable analysis,hepatocellular carcinoma
                Gastroenterology & Hepatology
                prognosis, multivariable analysis, hepatocellular carcinoma

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