The significance of cirrhosis in cases with intra-hepatic cholangiocarcinoma: A SEER-based retrospective cohort study

The significance of cirrhosis in cases with intra-hepatic cholangiocarcinoma: A SEER-based retrospective cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article The significance of cirrhosis in cases with intra-hepatic cholangiocarcinoma: A SEER-based retrospective cohort study Wen-Hui Wang, Hong-Jun Lin, Qing Lu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4629057/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective To systematically evaluate the significance of cirrhosis in cases of intrahepatic cholangiocarcinoma (IHCC) concerning short and long-term outcomes. Methods Cases diagnosed with IHCC from 2000 to 2020 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Comparative analyses were conducted between cases with cirrhosis and those without cirrhosis. Results A total of 644 cases with sufficient staging information and cirrhosis data were ultimately included. Comparative analyses indicated that cirrhosis was more prevalent among male cases (72.3% vs 50.6%, P < 0.001). Similar tumor differentiation status was observed between the two groups (P = 0.510). Cases without cirrhosis exhibited a higher incidence of T3-T4 disease (19.3% vs 12.2%, P = 0.025). Radiotherapy (3.3% vs 7.9%, P = 0.024), chemotherapy (45.5% vs 56.8%, P = 0.007), and surgery (37.1% vs 47.1%, P = 0.016) were more frequently performed among cases without cirrhosis. Cirrhosis was identified as a risk factor with minimal impact on survival but was not a prognostic factor. Even after matching, cases with cirrhosis still demonstrated a comparable long-term prognosis compared to those without cirrhosis. Conclusion Cirrhosis represents a risk factor rather than a prognostic factor for IHCC cases. While cirrhotic cases may have a lower resectability rate, their overall prognosis is similar to that of non-cirrhotic cases. Biological sciences/Cancer Biological sciences/Cancer/Cancer epidemiology intrahepatic cholangiocarcinoma cirrhosis surgery prognosis Figures Figure 1 Figure 2 Figure 3 Introduction Intrahepatic cholangiocarcinoma (IHCC) is a malignant tumor originating from the epithelial cells of the intrahepatic bile ducts. Previous researches have shown that the cases with IHCC regularly shared a worse prognosis than those with hepatocellular carcinoma (HCC)( 1 ). According to the latest 8th American Joint Committee on Cancer (AJCC) staging system, apart from three most common and significant prognostic factors, T stage, N stage, and M stage, concurrent liver cirrhosis has also been mentioned as a prognostic factor requiring for additional clinical care (AJCC level of evidence II). In theory, the liver function of patients with cirrhosis is usually worse than that of patients without cirrhosis. For patients with liver malignancies, cases with cirrhosis often could only tolerate a smaller range of surgical resection, share a lower chance of achieving the clear surgical margin, and therefore share a poorer prognosis. The significance of cirrhosis in cases with IHCC has been systematically evaluated by Wang J et al based on the public Surveillance, Epidemiology, and End Results (SEER) database( 2 ). Their results indicated that cirrhosis was not associated with a worse prognosis in cases with IHCC even after propensity score matching (PSM)( 2 ). Their study was performed based on an aged cohort (SEER databases, 2021). Only cases staged with the 7th AJCC staging system for IHCC were incorporated in their research. However, considering the similarities between 7th AJCC staging system and the combined 7th AJCC staging system for IHCC, cases staged based on these two staging systems could be furtherly incorporated and therefore more powerful evidence could be acquired. Consequently, current study was performed to provide an update analysis on the significance of cirrhosis in cases with IHCC. More in-depth analyses based on an extremely larger sample size would be performed for further exploration. Materials and methods Cohort information The SEER database is the largest publicly-available cancer database, covering almost 28% American population( 3 ). Patients’ clinic-pathological and survival information were extracted from the SEER Program ( www.seer.cancer.gov ) SEER*Stat database released in April 2023: version 8.4.1.2 (with SEER Plus data). Only cases diagnosed with IHCC with adequate cirrhosis information were considered eligible. Cases with adequate staging information who staged by 7th AJCC staging criteria [ Derived AJCC TNM, 7th ed (2010–2015) and those staged by the combined Derived SEER Combined pTNM (2016–2017) ] were incorporated. T categories were classified into T1-T2 and T3-T4. N stages were also toughly classified into node negative (N-) and node positive (N+). The specific process of cases selection and identification was summarized in Fig. 1 . Variables identification A total of thirteen variables were incorporated, including diagnosis age, sex, race, marital status, concurrent liver cirrhosis, T stage, N stage, M stage, tumor differentiation status, pathological subtypes, adjuvant radiotherapy, adjuvant chemotherapy, surgery, and cancer specific-survival (CSS). The continuous data “Age” was classified into categorical variables: ≤60 and > 60. Minor adjustments were also applied in other categorical variables. For example, previous researches have revealed the relationship between marital status and the overall prognosis of cases with various cancers( 4 – 6 ). Therefore, the variable “marital status” has also been incorporated into the current research. Race was simplified into three groups: Asian, White, Black/others. Statistical analysis The statistical analysis was conducted using R software version 4.2.2. The R package "tableone" was utilized for baseline comparisons and generating subsequent table outputs. Categorical data are presented as numbers (percentages). Categorical variables were assessed using Chi-Squared and Fisher’s exact tests. Survival analyses were performed using the R packages "survminer" and "survival." Kaplan–Meier curves and the corresponding risk table were visualized using the R command "ggsurvplot." Overall survival (OS) was defined as the time between the date of radical surgery and the date of death or last follow-up. Cancer-specific survival (CSS) was defined as the time from the date of radical surgery to the date of death due to cancer progression. Cox-proportional hazards models were constructed with the R packages "survminer," "dplyr," "survival," and "rms," presenting the hazard ratio (HR) and its 95% confidence interval (CI). Statistical significance was determined by P values less than 0.05. To evaluate the significance of cirrhosis among cases with IHCC more independently, a PSM analysis was performed (R package MatchIt, method="nearest", caliper = 0.05, ratio = 2) . Matching factors mainly included factors age, sex and other common independent prognostic factors for OS and CSS. Results Comparative analyses between cases with cirrhosis and those without cirrhosis in terms of clinic-pathological features and long-term survival A total of 644 cases diagnosed with IHCC with clear cirrhosis information were finally included. Regarding clinic-pathological features, as is summarized in Table 1, comparable age status (P = 0.566) and racial status (P = 0.118) were detected between cases with cirrhosis and those without cirrhosis. However, cirrhosis was more frequently detected among male cases (72.3% vs 50.6%, P < 0.001). Comparable tumor differentiation status was acquired between two groups (P = 0.510). Cases with cirrhosis shared a higher incidence with other pathological subtypes (except for pure adenocarcinoma) (P = 0.005). Cases without cirrhosis shared a higher incidence with T3-T4 disease (19.3% vs 12.2%, P = 0.025). Radiotherapy (P = 0.024), chemotherapy (P = 0.007), and surgery (P = 0.016) were more frequently performed among cases with cirrhosis. Regarding long-term outcomes, as is presented in Fig. 2 , comparable survival outcomes (OS and CSS) were acquired between cases with cirrhosis and those without cirrhosis, even when stratified by different surgery status (Fig. 2 A- 2 F). Univariate and multi-variate cox regression for prognostic and independent prognostic factors for OS and CSS We firstly analyzed all potential prognostic factors and independent prognostic factors for OS and CSS of the entire cohort. As is summarized in Table 2, marital status (married vs single/unknown) (P = 0.005), tumor differentiation grade (well to moderate vs poorly to undifferentiated vs unknown) (P < 0.001), T stage (T1-T2 vs T3-T4) (P < 0.001), N stage (N- vs N+) (P < 0.001), M stage (M- vs M+) (P < 0.001), pathological subtypes (adenocarcinoma vs others) (P = 0.017), radiotherapy (P = 0.003), and surgery (not performed vs performed) (P < 0.001) were prognostic factors for OS. T stage, N stage, M stage, tumor differentiation status, and surgery were independent prognostic factors for OS. Similar observations have also been detected in the relevant analyses for CSS. However, chemotherapy was found to be a prognostic factor for CSS (P = 0.017) while pathological subtypes (P = 0.302) and T stage (P = 0.059) failed to be of statistical significance. Chemotherapy was also found to be an independent prognostic factor for CSS (P < 0.001). Cirrhosis was found to be a risk factor (HR < 1) but not a prognostic factor either for OS or CSS (Table 2). Subsequently, subgroup analyses were performed based on different surgery status. As is summarized in Table 3, for resected IHCC cases, T stage, N stage, and M stage were found to be prognostic factors as well as independent prognostic factors for OS and CSS. For unresectable cases, T stage, N stage, M stage, chemotherapy, and tumor differentiation status were found to be independent prognostic factors for OS. However, only sex, N stage, M stage, and chemotherapy were independent prognostic factors for CSS for unresectable cases. Cirrhosis was also a risk factor but not a prognostic factor either for resected or unresectable IHCC cases in terms of OS or CSS (Table 3). Propensity score matching analyses In order to furtherly evaluate the prognostic significance of cirrhosis as well as to avoid the survival impact brought by other confounding factors, the PSM analyses were performed via controlling age, sex, and other common independent prognostic factors for OS and CSS (T stage, N stage, tumor differentiation grade, and surgery) (ratio 1:1, caliper 0.1). As is summarized in Table 4, after matching, all variables, except for racial status and chemotherapy, reached a balanced status (Table 4). Similar survival analyses were performed and the results were consistent with findings before PSM that cirrhosis has little impact on the overall prognosis, including OS and CSS (Fig. 3 A- 3 F) Discussion Our study represents the most compelling exploration to date on the prognostic value of cirrhosis in patients with IHCC. In comparison to previous research on the same topic conducted by Wang J et al, our study included a larger number of cases (644 vs. 398). Furthermore, we conducted subgroup analyses based on different surgical statuses to identify prognostic factors and independent predictors for OS and CSS. The findings from this study are expected to offer valuable clinical insights into the prognostic significance of cirrhosis among patients with IHCC. Hepatitis-derived cirrhosis, especially for cases with HBV infection, has been demonstrated as the major risk factor for the development and prognosis of cases with HCC( 7 ). The latest 8th AJCC staging system has also indicated that cirrhosis should be a risk factor requiring for additional clinical care among IHCC cases while the potential mechanism of cirrhosis in cases with IHCC remains elusive. For IHCC patients, recurrent hepatolithiasis accompanied by cholangitis could facilitate the development of liver fibrosis, cirrhosis, and atypical proliferation of intrahepatic bile duct epithelial cells, which are important risk factors in the development and progression of IHCC. Pathological changes in the liver parenchyma and hepatic blood flow contribute to a decline in hepatocyte function and an elevation in transhepatic vascular resistance, leading to the development of portal hypertension( 8 ). As many as 20% of patients with cirrhosis might finally develop HCC( 8 ). Various life-threatening complications, such as bleeding from esophageal varices, ascites, spontaneous bacterial peritonitis, and hepatic encephalopathy, could be frequently detected among cases with advanced cirrhotic disease. Curative-surgery with negative surgical margin has always been the most effective method for the tumor clearance and achieving long-term survival while existing evidence has suggested that cirrhotic liver shared a higher incidence of postoperative liver disfunction after hepatectomy( 9 – 11 ). The complications mentioned above can be surgical contraindications for cases requiring partial hepatectomy because of liver malignancies or benign liver tumors. Based on the guidelines from the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD) regarding therapeutic regimes for HCC, partial hepatectomy is only applicable to cases with favorable liver functions, especially for cirrhotic cases without portal hypertension( 12 ). Similar recommendation has also been illustrated in the Barcelona Clinic Liver Cancer (BCLC) classification system( 13 ). Therefore, based on the evidence above, for patients with liver malignancies, the presence of cirrhosis could significantly reduce the overall resectability rate, which has been demonstrated in our research that cases with cirrhosis shared a much lower surgery rate than those without cirrhosis (P = 0.016). Moreover, cirrhosis itself could also increase the overall risk of surgery and anesthesia, and contribute to the unfavorable postoperative recovery and long-term prognosis. The HR of cirrhosis in our research is higher than 1, suggesting that cirrhosis itself is a risk factor, which was consistent with findings by Wang J et al( 2 ) and Wei T et al( 14 ). Comparable long-term survival was acquired between cases with cirrhosis and those without cirrhosis even after matching, suggesting that the survival impact of cirrhosis is limited among IHCC cases and the actual factors determining the overall prognosis is the tumor stage, which has also been validated in previous publications( 2 , 14 ). Several limitations of our research should be furtherly illustrated. Firstly, current study was performed based on a retrospective cohort. The inherent selection bias can not be avoided, which might cause uncontrolled survival impact. Secondly, the definition of cirrhosis in the SEER database should also be furtherly illustrated and grouped. Whether a more precise and accurate classification criteria for cirrhosis would illustrate the impact of cirrhosis for IHCC cases should be furtherly explored. Thirdly, only several short-term outcomes have been evaluated in our research. Many other cirrhosis-related clinical outcomes, such as surgical margins, postoperative complications, mortalities, postoperative hospital stay, or recovery, should also be furtherly evaluated. However, the inadequate original data of SEER database has hindered us from further exploration. Conclusion Cirrhosis was a risk factor for IHCC cases and was associated with a lower overall resectability rate. However, cirrhosis failed to contribute to statistically-significant survival impact for cases with IHCC. More powerful in-detailed studies are required for further exploration. Abbreviations IHCC: intrahepatic cholangiocarcinoma HCC: hepatocellular carcinoma AJCC: American Joint Committee on Cancer SEER: Surveillance, Epidemiology, and End Results PSM: propensity score matching HR: hazard ratio CI: confidence interval Declarations Author contributions: Wen-Hui Wang and Hong-Jun Lin contributed equally to the study. Hong-Jun Lin contributed to data acquisition and drafted the manuscript. Qiang Lu contributed to the literature review, manuscript editing and subsequent minor revision. Qiang Lu also was involved in editing the manuscript. Wen-Hui Wang and Qiang Lu contributed to the study design and revision of the manuscript. Funding: Research on the enhancement of HIFU using Mn-based conjugated enzyme mimetics for tissue ablation therapy in the treatment of liver cancer (2022NSFSC0835Mn) Conflicts of interest: All authors declare have no conflicts of interest to disclose. Data availability statement: All data generated or analyzed during this study is from the SEER database and can be provided if required (please contact the first author). References Lee YT, Wang JJ, Luu M, Noureddin M, Nissen NN, Patel TC, et al. Comparison of Clinical Features and Outcomes Between Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma in the United States. Hepatology (Baltimore, Md). 2021;74(5):2622–32. Wang J, Qiu Y, Yang Y, Shen S, Zhi M, Zhang B, et al. Impact of cirrhosis on long-term survival outcomes of patients with intrahepatic cholangiocarcinoma. Cancer medicine. 2022;11(19):3633–42. Mao W, Zhang Z, Huang X, Fan J, Geng J. Marital Status and Survival in Patients with Penile Cancer. Journal of Cancer. 2019;10(12):2661–9. Tao L, Pan X, Zhang L, Wang J, Zhang Z, Zhang L, et al. Marital Status and Prognostic Nomogram for Bladder Cancer With Distant Metastasis: A SEER-Based Study. Frontiers in oncology. 2020;10:586458. Wu Y, Zhu PZ, Chen YQ, Chen J, Xu L, Zhang H. Relationship between marital status and survival in patients with lung adenocarcinoma: A SEER-based study. Medicine. 2022;101(1):e28492. Zhou C, Zhang Y, Hu X, Fang M, Xiao S. The effect of marital and insurance status on the survival of elderly patients with stage M1b colon cancer: a SEER-based study. BMC cancer. 2021;21(1):891. Bengtsson B, Widman L, Wahlin S, Stål P, Björkström NK, Hagström H. The risk of hepatocellular carcinoma in cirrhosis differs by etiology, age and sex: A Swedish nationwide population-based cohort study. United European gastroenterology journal. 2022;10(5):465–76. Schuppan D, Afdhal NH. Liver cirrhosis. Lancet (London, England). 2008;371(9615):838–51. Chan A, Kow A, Hibi T, Di Benedetto F, Serrablo A. Liver resection in Cirrhotic liver: Are there any limits? International journal of surgery (London, England). 2020;82s:109 – 14. Søreide JA, Deshpande R. Post hepatectomy liver failure (PHLF) - Recent advances in prevention and clinical management. European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2021;47(2):216–24. Li YY, Li H, Lv P, Liu G, Li XR, Tian BN, et al. Prognostic value of cirrhosis for intrahepatic cholangiocarcinoma after surgical treatment. Journal of gastrointestinal surgery: official journal of the Society for Surgery of the Alimentary Tract. 2011;15(4):608–13. Berzigotti A, Reig M, Abraldes JG, Bosch J, Bruix J. Portal hypertension and the outcome of surgery for hepatocellular carcinoma in compensated cirrhosis: a systematic review and meta-analysis. Hepatology (Baltimore, Md). 2015;61(2):526–36. Eguchi S, Kanematsu T, Arii S, Omata M, Kudo M, Sakamoto M, et al. Recurrence-free survival more than 10 years after liver resection for hepatocellular carcinoma. The British journal of surgery. 2011;98(4):552–7. Wei T, Zhang XF, He J, Popescu I, Marques HP, Aldrighetti L, et al. Prognostic impact of perineural invasion in intrahepatic cholangiocarcinoma: multicentre study. The British journal of surgery. 2022;109(7):610–6. Tables Tables 1 to 4 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1.docx Table2.docx Table3.docx Table4.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4629057","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":322083454,"identity":"23bb8e3a-73d5-4dfe-bc94-3dbac3647712","order_by":0,"name":"Wen-Hui Wang","email":"","orcid":"","institution":"West China Hospital of Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Wen-Hui","middleName":"","lastName":"Wang","suffix":""},{"id":322083456,"identity":"982fc14b-1f8d-4d3a-bf62-3482c62e15a7","order_by":1,"name":"Hong-Jun Lin","email":"","orcid":"","institution":"West China Hospital of Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Hong-Jun","middleName":"","lastName":"Lin","suffix":""},{"id":322083457,"identity":"cd6e3ffd-d15b-4656-a62d-b5fb9a301456","order_by":2,"name":"Qing Lu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAy0lEQVRIiWNgGAWjYBACPiA+AMRyEC4bEVrYoFqMSdMCAokNxGuRSN544OeO2vT57WcMGD6UHWbgn91ASEtawcHeM8dzN5zJMWCcce4wg8SdA4S05Bgc4G07lrtBgseAmbftMIOBRAJhLQf/th1Ll58B1PKXWC2HedtqEhhuALUwEqWF51nBYdm2A4YbzgA91XMunUfiBgEt/OzJmz++bauTl28/vPHBjzJrOf4ZBLQAgQEQHwazDgAxD0H1UC11xCgcBaNgFIyCkQoAqvxBrR/NTokAAAAASUVORK5CYII=","orcid":"","institution":"West China Hospital of Sichuan University","correspondingAuthor":true,"prefix":"","firstName":"Qing","middleName":"","lastName":"Lu","suffix":""}],"badges":[],"createdAt":"2024-06-24 09:30:45","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4629057/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4629057/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":60709267,"identity":"2b67f9bb-56d9-450b-8521-9293c8765b02","added_by":"auto","created_at":"2024-07-19 19:53:36","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":21882,"visible":true,"origin":"","legend":"\u003cp\u003eSpecific process of cases selection and identification\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4629057/v1/0246c73de864c099a69d6af9.jpg"},{"id":60709268,"identity":"05b74ccb-aab6-459a-be07-e005434e3522","added_by":"auto","created_at":"2024-07-19 19:53:36","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":399775,"visible":true,"origin":"","legend":"\u003cp\u003eKM curves presenting survival outcomes between IHCC cases with cirrhosis and those without cirrhosis before PSM. A, OS of the entire cohort; B, OS of cases who received surgery; C, OS of cases who failed to receive surgery; D, CSS of the entire cohort; E, CSS of cases who received surgery; F, CSS of cases who failed to receive surgery. OS: overall survival. CSS: cancer-specific survival. IHCC: intrahepatic cholangiocarcinoma. PSM: propensity score matching.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4629057/v1/1366b656bbb76f0e39a2e3bc.png"},{"id":60709272,"identity":"9b8cd6f7-96dc-4b59-9ddd-cc4eaa165588","added_by":"auto","created_at":"2024-07-19 19:53:36","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":400329,"visible":true,"origin":"","legend":"\u003cp\u003eKM curves presenting survival outcomes between IHCC cases with cirrhosis and those without cirrhosis after PSM. A, OS of the entire cohort; B, OS of cases who received surgery; C, OS of cases who failed to receive surgery; D, CSS of the entire cohort; E, CSS of cases who received surgery; F, CSS of cases who failed to receive surgery. OS: overall survival. CSS: cancer-specific survival. IHCC: intrahepatic cholangiocarcinoma. 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Previous researches have shown that the cases with IHCC regularly shared a worse prognosis than those with hepatocellular carcinoma (HCC)(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). According to the latest 8th American Joint Committee on Cancer (AJCC) staging system, apart from three most common and significant prognostic factors, T stage, N stage, and M stage, concurrent liver cirrhosis has also been mentioned as a prognostic factor requiring for additional clinical care (AJCC level of evidence II). In theory, the liver function of patients with cirrhosis is usually worse than that of patients without cirrhosis. For patients with liver malignancies, cases with cirrhosis often could only tolerate a smaller range of surgical resection, share a lower chance of achieving the clear surgical margin, and therefore share a poorer prognosis. The significance of cirrhosis in cases with IHCC has been systematically evaluated by Wang J et al based on the public Surveillance, Epidemiology, and End Results (SEER) database(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Their results indicated that cirrhosis was not associated with a worse prognosis in cases with IHCC even after propensity score matching (PSM)(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Their study was performed based on an aged cohort (SEER databases, 2021). Only cases staged with the 7th AJCC staging system for IHCC were incorporated in their research. However, considering the similarities between 7th AJCC staging system and the combined 7th AJCC staging system for IHCC, cases staged based on these two staging systems could be furtherly incorporated and therefore more powerful evidence could be acquired. Consequently, current study was performed to provide an update analysis on the significance of cirrhosis in cases with IHCC. More in-depth analyses based on an extremely larger sample size would be performed for further exploration.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eCohort information\u003c/h2\u003e \u003cp\u003eThe SEER database is the largest publicly-available cancer database, covering almost 28% American population(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Patients\u0026rsquo; clinic-pathological and survival information were extracted from the SEER Program (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e\u003ca href=\"http://www.seer.cancer.gov\" target=\"_blank\"\u003ewww.seer.cancer.gov\u003c/a\u003e\u003c/span\u003e\u003cspan address=\"http://www.seer.cancer.gov\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cem\u003e)\u003c/em\u003e SEER*Stat database released in April 2023: version 8.4.1.2 (with SEER Plus data). Only cases diagnosed with IHCC with adequate cirrhosis information were considered eligible. Cases with adequate staging information who staged by 7th AJCC staging criteria [\u003cem\u003eDerived AJCC TNM, 7th ed (2010\u0026ndash;2015)\u003c/em\u003e and those staged by the \u003cem\u003ecombined Derived SEER Combined pTNM (2016\u0026ndash;2017)\u003c/em\u003e] were incorporated. T categories were classified into T1-T2 and T3-T4. N stages were also toughly classified into node negative (N-) and node positive (N+). The specific process of cases selection and identification was summarized in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eVariables identification\u003c/h2\u003e \u003cp\u003eA total of thirteen variables were incorporated, including diagnosis age, sex, race, marital status, concurrent liver cirrhosis, T stage, N stage, M stage, tumor differentiation status, pathological subtypes, adjuvant radiotherapy, adjuvant chemotherapy, surgery, and cancer specific-survival (CSS). The continuous data \u0026ldquo;Age\u0026rdquo; was classified into categorical variables: \u0026le;60 and \u0026gt;\u0026thinsp;60. Minor adjustments were also applied in other categorical variables. For example, previous researches have revealed the relationship between marital status and the overall prognosis of cases with various cancers(\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Therefore, the variable \u0026ldquo;marital status\u0026rdquo; has also been incorporated into the current research. Race was simplified into three groups: Asian, White, Black/others.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe statistical analysis was conducted using R software version 4.2.2. The R package \"tableone\" was utilized for baseline comparisons and generating subsequent table outputs. Categorical data are presented as numbers (percentages). Categorical variables were assessed using Chi-Squared and Fisher\u0026rsquo;s exact tests. Survival analyses were performed using the R packages \"survminer\" and \"survival.\" Kaplan\u0026ndash;Meier curves and the corresponding risk table were visualized using the R command \"ggsurvplot.\" Overall survival (OS) was defined as the time between the date of radical surgery and the date of death or last follow-up. Cancer-specific survival (CSS) was defined as the time from the date of radical surgery to the date of death due to cancer progression. Cox-proportional hazards models were constructed with the R packages \"survminer,\" \"dplyr,\" \"survival,\" and \"rms,\" presenting the hazard ratio (HR) and its 95% confidence interval (CI). Statistical significance was determined by P values less than 0.05.\u003c/p\u003e \u003cp\u003eTo evaluate the significance of cirrhosis among cases with IHCC more independently, a PSM analysis was performed \u003cem\u003e(R package MatchIt, method=\"nearest\", caliper\u0026thinsp;=\u0026thinsp;0.05, ratio\u0026thinsp;=\u0026thinsp;2)\u003c/em\u003e. Matching factors mainly included factors age, sex and other common independent prognostic factors for OS and CSS.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e \u003cb\u003eComparative analyses between cases with cirrhosis and those without cirrhosis in terms of clinic-pathological features and long-term survival\u003c/b\u003e \u003c/p\u003e \u003cp\u003eA total of 644 cases diagnosed with IHCC with clear cirrhosis information were finally included. Regarding clinic-pathological features, as is summarized in Table\u0026nbsp;1, comparable age status (P\u0026thinsp;=\u0026thinsp;0.566) and racial status (P\u0026thinsp;=\u0026thinsp;0.118) were detected between cases with cirrhosis and those without cirrhosis. However, cirrhosis was more frequently detected among male cases (72.3% vs 50.6%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Comparable tumor differentiation status was acquired between two groups (P\u0026thinsp;=\u0026thinsp;0.510). Cases with cirrhosis shared a higher incidence with other pathological subtypes (except for pure adenocarcinoma) (P\u0026thinsp;=\u0026thinsp;0.005). Cases without cirrhosis shared a higher incidence with T3-T4 disease (19.3% vs 12.2%, P\u0026thinsp;=\u0026thinsp;0.025). Radiotherapy (P\u0026thinsp;=\u0026thinsp;0.024), chemotherapy (P\u0026thinsp;=\u0026thinsp;0.007), and surgery (P\u0026thinsp;=\u0026thinsp;0.016) were more frequently performed among cases with cirrhosis. Regarding long-term outcomes, as is presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e2\u003c/span\u003e, comparable survival outcomes (OS and CSS) were acquired between cases with cirrhosis and those without cirrhosis, even when stratified by different surgery status (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e2\u003c/span\u003eA-\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e2\u003c/span\u003eF).\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eUnivariate and multi-variate cox regression for prognostic and independent prognostic factors for OS and CSS\u003c/h2\u003e \u003cp\u003eWe firstly analyzed all potential prognostic factors and independent prognostic factors for OS and CSS of the entire cohort. As is summarized in Table\u0026nbsp;2, marital status (married vs single/unknown) (P\u0026thinsp;=\u0026thinsp;0.005), tumor differentiation grade (well to moderate vs poorly to undifferentiated vs unknown) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), T stage (T1-T2 vs T3-T4) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), N stage (N- vs N+) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), M stage (M- vs M+) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), pathological subtypes (adenocarcinoma vs others) (P\u0026thinsp;=\u0026thinsp;0.017), radiotherapy (P\u0026thinsp;=\u0026thinsp;0.003), and surgery (not performed vs performed) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were prognostic factors for OS. T stage, N stage, M stage, tumor differentiation status, and surgery were independent prognostic factors for OS. Similar observations have also been detected in the relevant analyses for CSS. However, chemotherapy was found to be a prognostic factor for CSS (P\u0026thinsp;=\u0026thinsp;0.017) while pathological subtypes (P\u0026thinsp;=\u0026thinsp;0.302) and T stage (P\u0026thinsp;=\u0026thinsp;0.059) failed to be of statistical significance. Chemotherapy was also found to be an independent prognostic factor for CSS (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Cirrhosis was found to be a risk factor (HR\u0026thinsp;\u0026lt;\u0026thinsp;1) but not a prognostic factor either for OS or CSS (Table\u0026nbsp;2).\u003c/p\u003e \u003cp\u003eSubsequently, subgroup analyses were performed based on different surgery status. As is summarized in Table\u0026nbsp;3, for resected IHCC cases, T stage, N stage, and M stage were found to be prognostic factors as well as independent prognostic factors for OS and CSS. For unresectable cases, T stage, N stage, M stage, chemotherapy, and tumor differentiation status were found to be independent prognostic factors for OS. However, only sex, N stage, M stage, and chemotherapy were independent prognostic factors for CSS for unresectable cases. Cirrhosis was also a risk factor but not a prognostic factor either for resected or unresectable IHCC cases in terms of OS or CSS (Table\u0026nbsp;3).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePropensity score matching analyses\u003c/h2\u003e \u003cp\u003eIn order to furtherly evaluate the prognostic significance of cirrhosis as well as to avoid the survival impact brought by other confounding factors, the PSM analyses were performed via controlling age, sex, and other common independent prognostic factors for OS and CSS (T stage, N stage, tumor differentiation grade, and surgery) (ratio 1:1, caliper 0.1). As is summarized in Table\u0026nbsp;4, after matching, all variables, except for racial status and chemotherapy, reached a balanced status (Table\u0026nbsp;4). Similar survival analyses were performed and the results were consistent with findings before PSM that cirrhosis has little impact on the overall prognosis, including OS and CSS (Fig.\u0026nbsp;\u003cspan refid=\"Fig15\" class=\"InternalRef\"\u003e3\u003c/span\u003eA-\u003cspan refid=\"Fig15\" class=\"InternalRef\"\u003e3\u003c/span\u003eF)\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study represents the most compelling exploration to date on the prognostic value of cirrhosis in patients with IHCC. In comparison to previous research on the same topic conducted by Wang J et al, our study included a larger number of cases (644 vs. 398). Furthermore, we conducted subgroup analyses based on different surgical statuses to identify prognostic factors and independent predictors for OS and CSS. The findings from this study are expected to offer valuable clinical insights into the prognostic significance of cirrhosis among patients with IHCC.\u003c/p\u003e \u003cp\u003eHepatitis-derived cirrhosis, especially for cases with HBV infection, has been demonstrated as the major risk factor for the development and prognosis of cases with HCC(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). The latest 8th AJCC staging system has also indicated that cirrhosis should be a risk factor requiring for additional clinical care among IHCC cases while the potential mechanism of cirrhosis in cases with IHCC remains elusive. For IHCC patients, recurrent hepatolithiasis accompanied by cholangitis could facilitate the development of liver fibrosis, cirrhosis, and atypical proliferation of intrahepatic bile duct epithelial cells, which are important risk factors in the development and progression of IHCC. Pathological changes in the liver parenchyma and hepatic blood flow contribute to a decline in hepatocyte function and an elevation in transhepatic vascular resistance, leading to the development of portal hypertension(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). As many as 20% of patients with cirrhosis might finally develop HCC(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Various life-threatening complications, such as bleeding from esophageal varices, ascites, spontaneous bacterial peritonitis, and hepatic encephalopathy, could be frequently detected among cases with advanced cirrhotic disease. Curative-surgery with negative surgical margin has always been the most effective method for the tumor clearance and achieving long-term survival while existing evidence has suggested that cirrhotic liver shared a higher incidence of postoperative liver disfunction after hepatectomy(\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). The complications mentioned above can be surgical contraindications for cases requiring partial hepatectomy because of liver malignancies or benign liver tumors. Based on the guidelines from the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD) regarding therapeutic regimes for HCC, partial hepatectomy is only applicable to cases with favorable liver functions, especially for cirrhotic cases without portal hypertension(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Similar recommendation has also been illustrated in the Barcelona Clinic Liver Cancer (BCLC) classification system(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Therefore, based on the evidence above, for patients with liver malignancies, the presence of cirrhosis could significantly reduce the overall resectability rate, which has been demonstrated in our research that cases with cirrhosis shared a much lower surgery rate than those without cirrhosis (P\u0026thinsp;=\u0026thinsp;0.016). Moreover, cirrhosis itself could also increase the overall risk of surgery and anesthesia, and contribute to the unfavorable postoperative recovery and long-term prognosis. The HR of cirrhosis in our research is higher than 1, suggesting that cirrhosis itself is a risk factor, which was consistent with findings by Wang J et al(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) and Wei T et al(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Comparable long-term survival was acquired between cases with cirrhosis and those without cirrhosis even after matching, suggesting that the survival impact of cirrhosis is limited among IHCC cases and the actual factors determining the overall prognosis is the tumor stage, which has also been validated in previous publications(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSeveral limitations of our research should be furtherly illustrated. Firstly, current study was performed based on a retrospective cohort. The inherent selection bias can not be avoided, which might cause uncontrolled survival impact. Secondly, the definition of cirrhosis in the SEER database should also be furtherly illustrated and grouped. Whether a more precise and accurate classification criteria for cirrhosis would illustrate the impact of cirrhosis for IHCC cases should be furtherly explored. Thirdly, only several short-term outcomes have been evaluated in our research. Many other cirrhosis-related clinical outcomes, such as surgical margins, postoperative complications, mortalities, postoperative hospital stay, or recovery, should also be furtherly evaluated. However, the inadequate original data of SEER database has hindered us from further exploration.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eCirrhosis was a risk factor for IHCC cases and was associated with a lower overall resectability rate. However, cirrhosis failed to contribute to statistically-significant survival impact for cases with IHCC. More powerful in-detailed studies are required for further exploration.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eIHCC: intrahepatic cholangiocarcinoma\u003c/p\u003e\n\u003cp\u003eHCC: hepatocellular carcinoma\u003c/p\u003e\n\u003cp\u003eAJCC: American Joint Committee on Cancer\u003c/p\u003e\n\u003cp\u003eSEER: Surveillance, Epidemiology, and End Results\u003c/p\u003e\n\u003cp\u003ePSM: propensity score matching\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHR: hazard ratio\u003c/p\u003e\n\u003cp\u003eCI: confidence interval\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e Wen-Hui Wang\u0026nbsp;and\u0026nbsp;Hong-Jun Lin\u0026nbsp;contributed equally to the study.\u0026nbsp;Hong-Jun Lin\u0026nbsp;contributed to data acquisition and drafted the manuscript.\u0026nbsp;Qiang Lu contributed to the literature review, manuscript editing and subsequent minor revision. Qiang Lu also\u0026nbsp;was involved in editing the manuscript.\u0026nbsp;Wen-Hui Wang and Qiang Lu\u0026nbsp;contributed to the study design and revision of the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e Research on the enhancement of HIFU using Mn-based conjugated enzyme mimetics for tissue ablation therapy in the treatment of liver cancer (2022NSFSC0835Mn)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest:\u003c/strong\u003e All authors declare have no conflicts of interest to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement:\u003c/strong\u003e All data generated or analyzed during this study is from the SEER database and can be provided if required (please contact the first author).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLee YT, Wang JJ, Luu M, Noureddin M, Nissen NN, Patel TC, et al. Comparison of Clinical Features and Outcomes Between Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma in the United States. Hepatology (Baltimore, Md). 2021;74(5):2622\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang J, Qiu Y, Yang Y, Shen S, Zhi M, Zhang B, et al. Impact of cirrhosis on long-term survival outcomes of patients with intrahepatic cholangiocarcinoma. Cancer medicine. 2022;11(19):3633\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMao W, Zhang Z, Huang X, Fan J, Geng J. Marital Status and Survival in Patients with Penile Cancer. Journal of Cancer. 2019;10(12):2661\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTao L, Pan X, Zhang L, Wang J, Zhang Z, Zhang L, et al. Marital Status and Prognostic Nomogram for Bladder Cancer With Distant Metastasis: A SEER-Based Study. Frontiers in oncology. 2020;10:586458.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu Y, Zhu PZ, Chen YQ, Chen J, Xu L, Zhang H. Relationship between marital status and survival in patients with lung adenocarcinoma: A SEER-based study. Medicine. 2022;101(1):e28492.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou C, Zhang Y, Hu X, Fang M, Xiao S. The effect of marital and insurance status on the survival of elderly patients with stage M1b colon cancer: a SEER-based study. BMC cancer. 2021;21(1):891.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBengtsson B, Widman L, Wahlin S, St\u0026aring;l P, Bj\u0026ouml;rkstr\u0026ouml;m NK, Hagstr\u0026ouml;m H. The risk of hepatocellular carcinoma in cirrhosis differs by etiology, age and sex: A Swedish nationwide population-based cohort study. United European gastroenterology journal. 2022;10(5):465\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchuppan D, Afdhal NH. Liver cirrhosis. Lancet (London, England). 2008;371(9615):838\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChan A, Kow A, Hibi T, Di Benedetto F, Serrablo A. Liver resection in Cirrhotic liver: Are there any limits? International journal of surgery (London, England). 2020;82s:109\u0026thinsp;\u0026ndash;\u0026thinsp;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eS\u0026oslash;reide JA, Deshpande R. Post hepatectomy liver failure (PHLF) - Recent advances in prevention and clinical management. European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2021;47(2):216\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi YY, Li H, Lv P, Liu G, Li XR, Tian BN, et al. Prognostic value of cirrhosis for intrahepatic cholangiocarcinoma after surgical treatment. Journal of gastrointestinal surgery: official journal of the Society for Surgery of the Alimentary Tract. 2011;15(4):608\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBerzigotti A, Reig M, Abraldes JG, Bosch J, Bruix J. Portal hypertension and the outcome of surgery for hepatocellular carcinoma in compensated cirrhosis: a systematic review and meta-analysis. Hepatology (Baltimore, Md). 2015;61(2):526\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEguchi S, Kanematsu T, Arii S, Omata M, Kudo M, Sakamoto M, et al. Recurrence-free survival more than 10 years after liver resection for hepatocellular carcinoma. The British journal of surgery. 2011;98(4):552\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWei T, Zhang XF, He J, Popescu I, Marques HP, Aldrighetti L, et al. Prognostic impact of perineural invasion in intrahepatic cholangiocarcinoma: multicentre study. The British journal of surgery. 2022;109(7):610\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 4 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"intrahepatic cholangiocarcinoma, cirrhosis, surgery, prognosis","lastPublishedDoi":"10.21203/rs.3.rs-4629057/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4629057/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo systematically evaluate the significance of cirrhosis in cases of intrahepatic cholangiocarcinoma (IHCC) concerning short and long-term outcomes.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eCases diagnosed with IHCC from 2000 to 2020 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Comparative analyses were conducted between cases with cirrhosis and those without cirrhosis.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 644 cases with sufficient staging information and cirrhosis data were ultimately included. Comparative analyses indicated that cirrhosis was more prevalent among male cases (72.3% vs 50.6%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Similar tumor differentiation status was observed between the two groups (P\u0026thinsp;=\u0026thinsp;0.510). Cases without cirrhosis exhibited a higher incidence of T3-T4 disease (19.3% vs 12.2%, P\u0026thinsp;=\u0026thinsp;0.025). Radiotherapy (3.3% vs 7.9%, P\u0026thinsp;=\u0026thinsp;0.024), chemotherapy (45.5% vs 56.8%, P\u0026thinsp;=\u0026thinsp;0.007), and surgery (37.1% vs 47.1%, P\u0026thinsp;=\u0026thinsp;0.016) were more frequently performed among cases without cirrhosis. Cirrhosis was identified as a risk factor with minimal impact on survival but was not a prognostic factor. Even after matching, cases with cirrhosis still demonstrated a comparable long-term prognosis compared to those without cirrhosis.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eCirrhosis represents a risk factor rather than a prognostic factor for IHCC cases. While cirrhotic cases may have a lower resectability rate, their overall prognosis is similar to that of non-cirrhotic cases.\u003c/p\u003e","manuscriptTitle":"The significance of cirrhosis in cases with intra-hepatic cholangiocarcinoma: A SEER-based retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-19 19:53:31","doi":"10.21203/rs.3.rs-4629057/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d095bcef-a9e3-44cf-9a3f-435eb1694b05","owner":[],"postedDate":"July 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":34056132,"name":"Biological sciences/Cancer"},{"id":34056133,"name":"Biological sciences/Cancer/Cancer epidemiology"}],"tags":[],"updatedAt":"2025-10-03T20:23:22+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-19 19:53:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4629057","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4629057","identity":"rs-4629057","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}