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Fan W, Zheng X, Zhang W, Zhu B, Wu Y, Xue M, Tang R, Huang Z, Qiao L, Lu M, Wu J, Tang Y, Chen J, Huang S, Bai M, Li J. Prediction Model of Survival in Unresectable HCC with Central Bile Duct Invasion Receiving TACE After Biliary Drainage: TEMP Score. J Hepatocell Carcinoma 2025; 12:615-628. [PMID: 40130082 PMCID: PMC11932117 DOI: 10.2147/jhc.s505328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Accepted: 03/07/2025] [Indexed: 03/26/2025] Open
Abstract
Purpose Central bile duct invasion (BDI) by hepatocellular carcinoma (HCC) is rare and associated with poor prognosis, lacking treatment guidelines. While transarterial chemoembolization (TACE) is often used for unresectable cases, determining optimal candidates post-biliary drainage is controversial. We aim to develop a prognostic prediction model for unresectable HCC (uHCC) patients with central BDI receiving sequential TACE after successful biliary drainage. Patients and Methods We retrospectively analyzed 267 uHCC patients with central BDI receiving successful biliary drainage and sequential TACE from seven tertiary centers (2015-2021), divided into training (n=187) and validation (n=80) sets. Using Cox proportional-hazards regression model, we identified key prognostic indicators for overall survival (OS) and constructed a prediction model. Results Pre-TACE total bilirubin (TBil) values, extrahepatic spread (EHS), multiple intrahepatic tumors (MIT), and portal vein tumor thrombus (PVTT) were identified as the significant clinical indicators for OS. These four parameters were included in a novel prediction model, named TEMP score, which could successfully categorize patients in the training set into three distinct risk grades with median OS of 26.9, 9.4, and 5.8 months, respectively. The TEMP score predicted the time-dependent areas under the receiver operating characteristic curves for OS at 6 months, 1 year, and 2 years of 0.813/0.907, 0.833/0.782, and 0.838/0.811 in the training and validation sets, with corresponding C-indices of 0.812/0.929, 0.829/0.761, and 0.818/0.791, respectively, outperforming other currently available models in both cohorts. The calibration curve of the model for predicting OS presented good consistency between observations and predictions in both the training set and validation set. Conclusion The TEMP score effectively stratifies the prognosis of uHCC patients with central BDI who have undergone successful bile drainage and sequential TACE, helping to identify those who may benefit from TACE treatment.
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Affiliation(s)
- Wenzhe Fan
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Xinlin Zheng
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Weihong Zhang
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Bowen Zhu
- Department of Precision Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Yanqin Wu
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Miao Xue
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Rong Tang
- Department of Hepatopancreatobiliary Surgery, Hainan General Hospital, Haikou, People’s Republic of China
| | - Zhen Huang
- Department of Interventional Angiology, Huizhou First People’s Hospital, Huizhou, People’s Republic of China
| | - Liangliang Qiao
- Department of Interventional Oncology, Jinshazhou Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China
| | - Mingjian Lu
- Department of Radiology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, People’s Republic of China
| | - Jian Wu
- Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Yiyang Tang
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Jinghua Chen
- Cancer Center, Guangzhou Twelfth People’s Hospital, Guangzhou, People’s Republic of China
| | - Shugui Huang
- Department of General Surgery I, The First Affiliated Hospital of Guangzhou Pharmaceutical University, Guangzhou, People’s Republic of China
| | - Mingjun Bai
- Department of Interventional Radiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Jiaping Li
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China
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Groß S, Bitzer M, Albert J, Blödt S, Boda-Heggemann J, Borucki K, Brunner T, Caspari R, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Gebert J, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, Fougère CL, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Ott J, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ringe K, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schütte K, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Trojan J, van Thiel I, Utzig M, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wenzel G, Wildner D, Wörns MA, Galle P, Malek N. S3-Leitlinie Diagnostik und Therapie biliärer Karzinome – Langversion. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2025; 63:e82-e158. [PMID: 39919781 DOI: 10.1055/a-2460-6347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/09/2025]
Affiliation(s)
- Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | | | - Katrin Borucki
- Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Institut für Klinische Chemie und Pathobiochemie
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Jamila Gebert
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Julia Ott
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Digestive Diseases and Nutrition, Gastroenterology, University of Kentucky
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | - Kristina Ringe
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | | | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Kerstin Schütte
- Klinik für Innere Medizin und Gastroenterologie, Niels-Stensen-Kliniken, Marienhospital Osnabrück
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Martin Utzig
- Abteilung Zertifizierung, Deutsche Krebsgesellschaft e.V., Berlin
| | - Arndt Vogel
- Institute of Medical Science, University of Toronto
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Gregor Wenzel
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
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Sangro B, Argemi J, Ronot M, Paradis V, Meyer T, Mazzaferro V, Jepsen P, Golfieri R, Galle P, Dawson L, Reig M. EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. J Hepatol 2025; 82:315-374. [PMID: 39690085 DOI: 10.1016/j.jhep.2024.08.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 08/29/2024] [Indexed: 12/19/2024]
Abstract
Liver cancer is the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 90% of primary liver cancers. Advances in diagnostic and therapeutic tools, along with improved understanding of their application, are transforming patient treatment. Integrating these innovations into clinical practice presents challenges and necessitates guidance. These clinical practice guidelines offer updated advice for managing patients with HCC and provide a comprehensive review of pertinent data. Key updates from the 2018 EASL guidelines include personalised surveillance based on individual risk assessment and the use of new tools, standardisation of liver imaging procedures and diagnostic criteria, use of minimally invasive surgery in complex cases together with updates on the integrated role of liver transplantation, transitions between surgical, locoregional, and systemic therapies, the role of radiation therapies, and the use of combination immunotherapies at various stages of disease. Above all, there is an absolute need for a multiparametric assessment of individual risks and benefits, considering the patient's perspective, by a multidisciplinary team encompassing various specialties.
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Fu Y, Maccioni L, Wang XW, Greten TF, Gao B. Alcohol-associated liver cancer. Hepatology 2024; 80:1462-1479. [PMID: 38607725 DOI: 10.1097/hep.0000000000000890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 03/28/2024] [Indexed: 04/14/2024]
Abstract
Heavy alcohol intake induces a wide spectrum of liver diseases ranging from steatosis, steatohepatitis, cirrhosis, and HCC. Although alcohol consumption is a well-known risk factor for the development, morbidity, and mortality of HCC globally, alcohol-associated hepatocellular carcinoma (A-HCC) is poorly characterized compared to viral hepatitis-associated HCC. Most A-HCCs develop after alcohol-associated cirrhosis (AC), but the direct carcinogenesis from ethanol and its metabolites to A-HCC remains obscure. The differences between A-HCC and HCCs caused by other etiologies have not been well investigated in terms of clinical prognosis, genetic or epigenetic landscape, molecular mechanisms, and heterogeneity. Moreover, there is a huge gap between basic research and clinical practice due to the lack of preclinical models of A-HCC. In the current review, we discuss the pathogenesis, heterogeneity, preclinical approaches, epigenetic, and genetic profiles of A-HCC, and discuss the current insights into and the prospects for future research on A-HCC. The potential effect of alcohol on cholangiocarcinoma and liver metastasis is also discussed.
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Affiliation(s)
- Yaojie Fu
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
| | - Luca Maccioni
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
| | - Xin Wei Wang
- Liver Carcinogenesis Section, Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland, USA
- Liver Cancer Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA
| | - Tim F Greten
- Liver Cancer Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA
- Gastrointestinal Malignancies Section, Thoracic and Gastrointestinal Malignancies Branch, National Cancer Institute, NIH, Bethesda, Maryland, USA
| | - Bin Gao
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
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Song M, Tao Y, Zhang H, Du M, Guo L, Hu C, Zhang W. Gd-EOB-DTPA-enhanced MR imaging features of hepatocellular carcinoma in non-cirrhotic liver. Magn Reson Imaging 2024; 114:110241. [PMID: 39362318 DOI: 10.1016/j.mri.2024.110241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Revised: 09/17/2024] [Accepted: 09/29/2024] [Indexed: 10/05/2024]
Abstract
OBJECTIVE To evaluate clinical, pathological and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI) findings of hepatocellular carcinoma (HCC) in non-cirrhotic livers and compare with HCC in cirrhotic livers. METHODS This retrospective study included patients with pathologically confirmed HCC who underwent preoperative Gd-EOB-DTPA-enhanced MRI between January 2015 and October 2021. Propensity scores were utilized to match non-cirrhotic HCCs (NCHCCs) patients with cirrhotic HCCs (CHCCs) patients. The clinical, pathological and MR imaging features of NCHCCs were compared with CHCCs. Correlation between these features and the presence of NCHCCs were analyzed by logistic regression analysis. The predictive efficacy was evaluated using receiver operating characteristic (ROC) analysis. The area under the receiver operating characteristic curve (AUC) was used to compare performance, and the Delong test was used to compare AUCs. RESULTS After propensity score matching (1:3), a total of 144 patients with HCCs (36 NCHCCs and 108 CHCCs) were included. NCHCCs were larger in tumor size than CHCCs (P < 0.001, Cohen's d = 0.737). NCHCCs were more common in patients who have hepatitis C (5.6 % vs 1.9 %, P > 0.05) or have no known liver disease (11.1 % vs 0.9 %, P = 0.004), while hepatitis B was more common in CHCC patients (83.3 % vs 97.2 %, P = 0.003). Compared with CHCCs, NCHCCs more frequently demonstrated non-smooth tumor margin (P = 0.001, Cramer's V = 0.273), peri-tumoral hyperintensity (P < 0.05, Cramer's V = 0.185), hyperintense and heterogeneous signals in hepatobiliary phase (HBP) (P < 0.05). CHCCs were more likely to have satellite nodules compared to NCHCCs (33.3 % vs 57.4 %, P < 0.05, Cramer's V = 0.209). Based on the univariate and multivariate logistic regression analysis, the tumor size, non-smooth tumor margin, heterogeneous intensity in HBP and satellite nodule were significantly correlated to NCHCCs (P all <0.05). ROC curve analysis demonstrated that tumor size and non-smooth tumor margin were potential imaging predictors for the diagnosis of NCHCC, with AUC values of 0.715 and 0.639, respectively. The combination of the two imaging features for identifying NCHCC achieved an AUC value of 0.761, with a sensitivity of 0.889 and a specificity of 0.630. CONCLUSION NCHCCs were more likely to show larger tumor size, non-smooth tumor margin, peri-tumoral hyperintensity, as well as hyperintense and heterogeneous signals in HBP at Gd-EOB-DTPA-enhanced MR imaging compared with NCHCCs. Tumor size and non-smooth tumor margin in HBP may help to discriminate NCHCCs.
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Affiliation(s)
- Mingyue Song
- Department of Radiology, The Fourth Affiliated Hospital of Soochow University, Suzhou 215028, China; Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Yuhao Tao
- Department of Radiology, The Fourth Affiliated Hospital of Soochow University, Suzhou 215028, China; Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Hanjun Zhang
- Department of Radiology, The Fourth Affiliated Hospital of Soochow University, Suzhou 215028, China; Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Mingzhan Du
- Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Lingchuan Guo
- Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Chunhong Hu
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Weiguo Zhang
- Department of Radiology, The Fourth Affiliated Hospital of Soochow University, Suzhou 215028, China; Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
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Yu Q, Zhang Y, Ni J, Shen Y, Hu W. Identification and analysis of significant genes in nonalcoholic steatohepatitis-hepatocellular carcinoma transformation: Bioinformatics analysis and machine learning approach. Mol Immunol 2024; 174:18-31. [PMID: 39142007 DOI: 10.1016/j.molimm.2024.07.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2024] [Revised: 07/15/2024] [Accepted: 07/30/2024] [Indexed: 08/16/2024]
Abstract
PURPOSE Nonalcoholic steatohepatitis (NASH) has been an increasingly significant contributor to hepatocellular carcinoma (HCC). Understanding the progression from NASH to HCC is critical to early diagnosis and elucidating the underlying mechanisms. RESULTS 5 significant prognostic genes related to NASH-HCC transformation were identified through algorithm selection, which were ME1, TP53I3, SOCS2, GADD45G and CYP7A1. A diagnostic model for NASH prediction was established (AUC=0.988). TP53I3 and SOCS2 were selected as potential critical genes in the progression of NASH-HCC by external dataset validation and in vitro experiments on NASH and HCC cell lines. Immune infiltration analysis illustrated the correlation between 5 significant prognostic genes and immune cells. Single-cell analysis identified hepatocytes related to NASH-HCC transformation markers, revealing their promoting role in the transformation from NASH to HCC. CONCLUSION With bulk-seq analysis and single-cell analysis, 5 significant prognostic genes related to NASH-HCC transformation were identified and validated at both dataset and in vitro experiment level. Among them, TP53I3 and SOCS2 might be potential critical genes in NASH-HCC progression. Single-cell analysis identified and revealed the critical role that NASH-HCC related hepatocytes play in NASH-HCC tansformation. Our research may introduce a new perspective to the diagnosis, treatment of NASH-related HCC.
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Affiliation(s)
- Qiyi Yu
- Center for New Drug Safety Evaluation and Research, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China
| | - Yidong Zhang
- Center for New Drug Safety Evaluation and Research, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China
| | - Jiaping Ni
- Center for New Drug Safety Evaluation and Research, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China
| | - Yumeng Shen
- Center for New Drug Safety Evaluation and Research, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China.
| | - Weiwei Hu
- Center for New Drug Safety Evaluation and Research, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China; Lingang Laboratory, Shanghai 200032, China.
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Engstrand J, Stål P, Gilg S, Jansson A, Strömberg C. Hepatocellular carcinoma in cirrhotic versus non-cirrhotic liver: Treatment and survival differences in a nationwide cohort. Scand J Surg 2024; 113:120-130. [PMID: 38145321 DOI: 10.1177/14574969231220179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2023]
Abstract
BACKGROUND AND AIMS Numerous studies have reported superior outcome for patients with hepatocellular carcinoma (HCC) in non-cirrhotic compared to cirrhotic livers. This cohort study aims to describe the clinical presentation, disease course, treatment approaches, and survival differences in a population-based setting. METHODS Data on patients diagnosed with HCC in Sweden between 2008 and 2018 were identified and extracted from the Swedish Liver registry (SweLiv). Descriptive and survival statistics were applied. RESULTS Among the 4259 identified patients, 34% had HCC in a non-cirrhotic liver. Cirrhotic patients presented at a younger age (median = 64 vs 74 years, p < 0.001) and with a poorer performance status (Eastern Cooperative Oncology Group (ECOG) = 0-1: 64% vs 69%, p = 0.024). Underlying liver disease was more prevalent among cirrhotic patients (81% vs 19%, p < 0.001). Tumors in non-cirrhotic livers were diagnosed at a more advanced stage (T3-T4: 46% vs 31%) and more frequently with metastatic disease at diagnosis (22% vs 10%, p < 0.001). Tumors were significantly larger in non-cirrhotic livers (median size of largest tumor 7.5 cm) compared to cirrhotic livers (3.5 cm) (p < 0.001). Curative interventions were more commonly intended (45% vs 37%, p < 0.001) and performed (40% vs 31%, p < 0.001) in the cirrhotic vs non-cirrhotic patients. Median survival was 19 months (95% confidence interval (CI) = 18-21 months), in patients with cirrhosis as compared to 13 months in non-cirrhotic patients (95% CI = 11-15) (p < 0.001). In the multivariable Cox regression model, cirrhosis was not an independent predictor of survival, neither among curatively nor palliatively treated patients. CONCLUSION These population-based data show that patients with HCC in a cirrhotic liver receive curative treatment to a greater extent and benefit from superior survival compared to those with HCC in a non-cirrhotic liver. The differences in survival are more attributable to patient and tumor characteristics rather than the cirrhotic status itself. CLINICAL TRIAL REGISTRATION not applicable. Patient confidentially: not applicable.
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Affiliation(s)
- Jennie Engstrand
- Division of Surgery Department of Clinical Science, Intervention and Technology (CLINTEC) Karolinska Institutet and Karolinska University Hospital 141 86 Stockholm Sweden
| | - Per Stål
- Department of Gastroenterology and Hepatology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Stefan Gilg
- Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Anders Jansson
- Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Cecilia Strömberg
- Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
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8
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Ruiz E, Honles J, Fernández R, Uribe K, Cerapio JP, Cancino K, Contreras-Mancilla J, Casavilca-Zambrano S, Berrospi F, Pineau P, Bertani S. A preoperative risk score based on early recurrence for estimating outcomes after resection of hepatocellular carcinoma in the non-cirrhotic liver. HPB (Oxford) 2024; 26:691-702. [PMID: 38431511 DOI: 10.1016/j.hpb.2024.02.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 01/15/2024] [Accepted: 02/12/2024] [Indexed: 03/05/2024]
Abstract
BACKGROUND Liver resection is the mainstay treatment option for patients with hepatocellular carcinoma in the non-cirrhotic liver (NCL-HCC), but almost half of these patients will experience a recurrence within five years of surgery. Therefore, we aimed to develop a rationale-based risk evaluation tool to assist surgeons in recurrence-related treatment planning for NCL-HCC. METHODS We analyzed single-center data from 263 patients who underwent liver resection for NCL-HCC. Using machine learning modeling, we first determined an optimal cut-off point to discriminate early versus late relapses based on time to recurrence. We then constructed a risk score based on preoperative variables to forecast outcomes according to recurrence-free survival. RESULTS We computed an optimal cut-off point for early recurrence at 12 months post-surgery. We identified macroscopic vascular invasion, multifocal tumor, and spontaneous tumor rupture as predictor variables of outcomes associated with early recurrence and integrated them into a scoring system. We thus stratified, with high concordance, three groups of patients on a graduated scale of recurrence-related survival. CONCLUSION We constructed a preoperative risk score to estimate outcomes after liver resection in NCL-HCC patients. Hence, this score makes it possible to rationally stratify patients based on recurrence risk assessment for better treatment planning.
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Affiliation(s)
- Eloy Ruiz
- Departamento de Cirugía en Abdomen, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru; International Joint Laboratory of Molecular Anthropological Oncology, INEN, IRD, Lima, Peru.
| | - Jorge Honles
- International Joint Laboratory of Molecular Anthropological Oncology, INEN, IRD, Lima, Peru; UMR 152 PHARMADEV, Université de Toulouse, IRD, Toulouse, France
| | - Ramiro Fernández
- Departamento de Cirugía en Abdomen, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru; International Joint Laboratory of Molecular Anthropological Oncology, INEN, IRD, Lima, Peru
| | - Karla Uribe
- Departamento de Cirugía en Abdomen, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru
| | - Juan P Cerapio
- International Joint Laboratory of Molecular Anthropological Oncology, INEN, IRD, Lima, Peru; UMR 1037 CRCT, Université de Toulouse, INSERM, Toulouse, France
| | - Karina Cancino
- International Joint Laboratory of Molecular Anthropological Oncology, INEN, IRD, Lima, Peru; UMR 152 PHARMADEV, Université de Toulouse, IRD, Toulouse, France; UMR 1037 CRCT, Université de Toulouse, INSERM, Toulouse, France
| | - Juan Contreras-Mancilla
- International Joint Laboratory of Molecular Anthropological Oncology, INEN, IRD, Lima, Peru; Laboratorio de Investigación Traslacional y Biología Computacional, Universidad Peruana Cayetano Heredia, Lima, Peru
| | - Sandro Casavilca-Zambrano
- International Joint Laboratory of Molecular Anthropological Oncology, INEN, IRD, Lima, Peru; Departamento de Patología, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru; Facultad de Ciencias de la Salud, Universidad de Huánuco, Huánuco, Peru
| | - Francisco Berrospi
- Departamento de Cirugía en Abdomen, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru
| | - Pascal Pineau
- International Joint Laboratory of Molecular Anthropological Oncology, INEN, IRD, Lima, Peru; Unité Organisation Nucléaire et Oncogenèse, INSERM, Institut Pasteur, Paris, France
| | - Stéphane Bertani
- International Joint Laboratory of Molecular Anthropological Oncology, INEN, IRD, Lima, Peru; UMR 152 PHARMADEV, Université de Toulouse, IRD, Toulouse, France.
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9
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Jadzic J, Djonic D. Hepatocellular carcinoma and musculoskeletal system: A narrative literature review. World J Gastroenterol 2024; 30:2109-2117. [PMID: 38681992 PMCID: PMC11045483 DOI: 10.3748/wjg.v30.i15.2109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 02/07/2024] [Accepted: 03/26/2024] [Indexed: 04/19/2024] Open
Abstract
Musculoskeletal alterations in hepatocellular carcinoma (HCC) are less common than liver-related complications. However, they can significantly impact the quality of life and overall prognosis of patients with HCC. The main obstacle in the clinical assessment of HCC-induced musculoskeletal alterations is related to effective and timely diagnosis because these complications are often asymptomatic and unapparent during routine clinical evaluations. This narrative literature review aimed to provide a comprehensive overview of the contemporary literature related to the changes in the musculoskeletal system in patients with HCC, focusing on its clinical implications and underlying etiopathogenetic mechanisms. Osteolytic bone metastases are the most common skeletal alterations associated with HCC, which could be associated with an increased risk of low-trauma bone fracture. Moreover, previous studies reported that osteopenia, sarcopenia, and myosteatosis are associated with poor clinical outcomes in patients with HCC. Even though low bone mineral density and sarcopenia are consistently reported as reliable predictors of pretransplantation and post-transplantation mortality in HCC patients, these complications are frequently overlooked in the clinical management of patients with HCC. Taken together, contemporary literature suggests that a multidisciplinary approach is essential for early recognition and clinical management of HCC-associated musculoskeletal alterations to improve patient prognosis. Further research into the mechanisms and treatment options for musculoskeletal complications is warranted to enhance our understanding and clinical management of this aspect of HCC.
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Affiliation(s)
- Jelena Jadzic
- Center of Bone Biology, Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia
| | - Danijela Djonic
- Center of Bone Biology, Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia
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10
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Jadzic J, Djonic D. Hepatocellular carcinoma and musculoskeletal system: A narrative literature review. World J Gastroenterol 2024; 30:2109-2117. [DOI: https:/doi.org/10.3748/wjg.v30.i15.2109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/10/2024] Open
Abstract
Musculoskeletal alterations in hepatocellular carcinoma (HCC) are less common than liver-related complications. However, they can significantly impact the quality of life and overall prognosis of patients with HCC. The main obstacle in the clinical assessment of HCC-induced musculoskeletal alterations is related to effective and timely diagnosis because these complications are often asymptomatic and unapparent during routine clinical evaluations. This narrative literature review aimed to provide a comprehensive overview of the contemporary literature related to the changes in the musculoskeletal system in patients with HCC, focusing on its clinical implications and underlying etiopathogenetic mechanisms. Osteolytic bone metastases are the most common skeletal alterations associated with HCC, which could be associated with an increased risk of low-trauma bone fracture. Moreover, previous studies reported that osteopenia, sarcopenia, and myosteatosis are associated with poor clinical outcomes in patients with HCC. Even though low bone mineral density and sarcopenia are consistently reported as reliable predictors of pretransplantation and post-transplantation mortality in HCC patients, these complications are frequently overlooked in the clinical management of patients with HCC. Taken together, contemporary literature suggests that a multidisciplinary approach is essential for early recognition and clinical management of HCC-associated musculoskeletal alterations to improve patient prognosis. Further research into the mechanisms and treatment options for musculoskeletal complications is warranted to enhance our understanding and clinical management of this aspect of HCC.
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11
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Beudeker BJB, Guha R, Stoyanova K, IJzermans JNM, de Man RA, Sprengers D, Boonstra A. Cryptogenic non-cirrhotic HCC: Clinical, prognostic and immunologic aspects of an emerging HCC etiology. Sci Rep 2024; 14:4302. [PMID: 38383695 PMCID: PMC10881579 DOI: 10.1038/s41598-024-52884-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Accepted: 01/24/2024] [Indexed: 02/23/2024] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) in non-cirrhotic livers is rising significantly, but clear risk factors for screening remain elusive. This study sought to characterize non-cirrhotic HCC etiologies. HCC cases from 2009 to 2020 in a Dutch referral center were examined, revealing 371 out of 1654 cases (22%) as non-cirrhotic. Notably, the incidence of non-cirrhotic HCC increased by 61% in the time frame between 2009 and 2020. Interestingly 39% of non-cirrhotic HCC cases had cryptogenic origins. Cryptogenic non-cirrhotic HCC exhibited similarities with non-cirrhotic NAFLD HCC, but displayed advanced tumor stages, lower surgical rates, and a more frequent presence of symptoms, which substantiated in poor survival rates. Advanced cryptogenic non-cirrhotic HCC stages exhibited elevated serum interleukin-6 levels compared to non-cirrhotic HCC with defined etiologies. Comparative analysis encompassing cryptogenic and NAFLD non-cirrhotic HCC cohorts and controls unveiled comparable circulating immune biomarker profiles and PNPLA3 polymorphisms. To conclude, the primary etiology of non-cirrhotic HCC in our cohort has not defined risk factors. This cryptogenic variant exhibits distinct traits, such as advanced tumors and increased symptoms, and most resemble burned-out NAFLD. Understanding this HCC variant is crucial for improving screening and management strategies.
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Affiliation(s)
- Boris J B Beudeker
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Rael Guha
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Kalina Stoyanova
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Jan N M IJzermans
- Department of Surgery, Erasmus MC University Medical Center, Wytemaweg 80, 3015 CN Rotterdam, Postbus 2040, 3000 CA, Rotterdam, The Netherlands
| | - Robert A de Man
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Dave Sprengers
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Andre Boonstra
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
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12
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Groß S, Bitzer M, Albert J, Blödt S, Boda-Heggemann J, Brunner T, Caspari R, De Toni E, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, La Fougère C, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ritterbusch U, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Tholen R, Trojan J, van Thiel I, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wildner D, Wörns MA, Galle P, Malek N. S3-Leitlinie „Diagnostik und Therapie biliärer Karzinome“ – Langversion 4.0. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:e213-e282. [PMID: 38364849 DOI: 10.1055/a-2189-8567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/18/2024]
Affiliation(s)
- Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein, Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e. V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e. V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Klinik für Innere Medizin, Gesundheit Nord, Klinikverbund Bremen
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | | | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg
| | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Reina Tholen
- Deutscher Bundesverband für Physiotherapie (ZVK) e. V
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Arndt Vogel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
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13
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Aryan M, Ruli T, Shoreibah M. HCC in patients without cirrhosis: A review. Clin Liver Dis (Hoboken) 2024; 23:e0224. [PMID: 38872781 PMCID: PMC11168850 DOI: 10.1097/cld.0000000000000224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 03/28/2024] [Indexed: 06/15/2024] Open
Affiliation(s)
- Mahmoud Aryan
- Department of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Thomas Ruli
- Department of Internal Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Mohamed Shoreibah
- Department of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, Alabama, USA
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14
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Bitzer M, Groß S, Albert J, Blödt S, Boda-Heggemann J, Brunner T, Caspari R, De Toni E, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, Fougère CL, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ritterbusch U, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Tholen R, Trojan J, van Thiel I, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wildner D, Wörns MA, Galle P, Malek N. S3-Leitlinie „Diagnostik und Therapie des Hepatozellulären Karzinoms“ – Langversion 4.0. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:e67-e161. [PMID: 38195102 DOI: 10.1055/a-2189-6353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2024]
Affiliation(s)
- Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V.(AWMF), Berlin
| | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e. V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e. V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V.(AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Klinik für Innere Medizin, Gesundheit Nord, Klinikverbund Bremen
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | | | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | | | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Reina Tholen
- Deutscher Bundesverband für Physiotherapie (ZVK) e. V
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Arndt Vogel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
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White MJ, Jensen EH, Brauer DG. A Review of Resection and Surgical Ablation for Primary and Secondary Liver Cancers. Semin Intervent Radiol 2023; 40:536-543. [PMID: 38274223 PMCID: PMC10807965 DOI: 10.1055/s-0043-1777747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2024]
Abstract
The surgical management of primary and secondary liver tumors is constantly evolving. Patient selection, particularly with regard to determining resectability, is vital to the success of programs directed toward invasive treatments of liver tumors. Particular attention should be paid toward determining whether patients are best served with surgical resection or ablative therapies. A multidisciplinary approach is necessary to provide optimal care to patients with liver malignancy.
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Affiliation(s)
- McKenzie J. White
- Department of Surgery, University of Minnesota, Minneapolis, Minnesota
| | - Eric H. Jensen
- Department of Surgery, University of Minnesota, Minneapolis, Minnesota
- Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota
| | - David G. Brauer
- Department of Surgery, University of Minnesota, Minneapolis, Minnesota
- Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota
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16
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Schmidt M, Foster GR, Coppens M, Thomsen H, Dolmetsch R, Heijink L, Monahan PE, Pipe SW. Molecular evaluation and vector integration analysis of HCC complicating AAV gene therapy for hemophilia B. Blood Adv 2023; 7:4966-4969. [PMID: 37352263 PMCID: PMC10463188 DOI: 10.1182/bloodadvances.2023009876] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 05/23/2023] [Accepted: 06/13/2023] [Indexed: 06/25/2023] Open
Affiliation(s)
| | - Graham R. Foster
- Barts Liver Centre, Queen Mary University of London, London, United Kingdom
| | - Michiel Coppens
- Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Cardiovascular Sciences, Pulmonary Hypertension & Thrombosis, Amsterdam, The Netherlands
| | | | | | | | | | - Steven W. Pipe
- Departments of Pediatrics and Pathology, University of Michigan, Ann Arbor, MI
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17
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Reggidori N, Bucci L, Santi V, Stefanini B, Lani L, Rampoldi D, Ghittoni G, Farinati F, Masotto A, Stefanini B, Mega A, Biasini E, Foschi FG, Svegliati-Baroni G, Sangiovanni A, Campani C, Raimondo G, Vidili G, Gasbarrini A, Celsa C, Di Marco M, Giannini EG, Sacco R, Brunetto MR, Azzaroli F, Magalotti D, Morisco F, Rapaccini GL, Nardone G, Vitale A, Trevisani F. Landscape of alcohol-related hepatocellular carcinoma in the last 15 years highlights the need to expand surveillance programs. JHEP Rep 2023; 5:100784. [PMID: 37520672 PMCID: PMC10382941 DOI: 10.1016/j.jhepr.2023.100784] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 04/07/2023] [Accepted: 04/13/2023] [Indexed: 08/01/2023] Open
Abstract
BACKGROUND & AIMS Alcohol abuse and metabolic disorders are leading causes of hepatocellular carcinoma (HCC) worldwide. Alcohol-related aetiology is associated with a worse prognosis compared with viral agents, because of the lower percentage of patients diagnosed with HCC under routine surveillance and a higher burden of comorbidity in alcohol abusers. This study aimed to describe the evolving clinical scenario of alcohol-related HCC over 15 years (2006-2020) in Italy. METHODS Data from the Italian Liver Cancer (ITA.LI.CA) registry were used: 1,391 patients were allocated to three groups based on the year of HCC diagnosis (2006-2010; 2011-2015; 2016-2020). Patient characteristics, HCC treatment, and overall survival were compared among groups. Survival predictors were also investigated. RESULTS Approximately 80% of alcohol-related HCCs were classified as cases of metabolic dysfunction-associated fatty liver disease. Throughout the quinquennia, <50% of HCCs were detected by surveillance programmes. The tumour burden at diagnosis was slightly reduced but not enough to change the distribution of the ITA.LI.CA cancer stages. Intra-arterial and targeted systemic therapies increased across quinquennia. A modest improvement in survival was observed in the last quinquennia, particularly after 12 months of patient observation. Cancer stage, HCC treatment, and presence of oesophageal varices were independent predictors of survival. CONCLUSIONS In the past 15 years, modest improvements have been obtained in outcomes of alcohol-related HCC, attributed mainly to underuse of surveillance programmes and the consequent low amenability to curative treatments. Metabolic dysfunction-associated fatty liver disease is a widespread condition in alcohol abusers, but its presence did not show a pivotal prognostic role once HCC had developed. Instead, the presence of oesophageal varices, an independent poor prognosticator, should be considered in patient management and refining of prognostic systems. IMPACT AND IMPLICATIONS Alcohol abuse is a leading and growing cause of hepatocellular carcinoma (HCC) worldwide and is associated with a worse prognosis compared with other aetiologies. We assessed the evolutionary landscape of alcohol-related HCC over 15 years in Italy. A high cumulative prevalence (78%) of metabolic dysfunction-associated fatty liver disease, with signs of metabolic dysfunction, was observed in HCC patients with unhealthy excessive alcohol consumption. The alcohol + metabolic dysfunction-associated fatty liver disease condition tended to progressively increase over time. A modest improvement in survival occurred over the study period, likely because of the persistent underuse of surveillance programmes and, consequently, the lack of improvement in the cancer stage at diagnosis and the patients' eligibility for curative treatments. Alongside the known prognostic factors for HCC (cancer stage and treatment), the presence of oesophageal varices was an independent predictor of poor survival, suggesting that this clinical feature should be carefully considered in patient management and should be included in prognostic systems/scores for HCC to improve their performance.
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Affiliation(s)
- Nicola Reggidori
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Laura Bucci
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Valentina Santi
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Benedetta Stefanini
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Lorenzo Lani
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Davide Rampoldi
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | | | - Fabio Farinati
- Department of Surgery, Oncology, and Gastroenterology, Gastroenterology Unit, University of Padova, Padua, Italy
| | - Alberto Masotto
- Gastroenterology Unit, Ospedale Sacro Cuore Don Calabria, Negrar, Italy
| | - Bernardo Stefanini
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Andrea Mega
- Gastroenterology Unit, Bolzano Regional Hospital, Bolzano, Italy
| | - Elisabetta Biasini
- Infectious Diseases and Hepatology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Francesco Giuseppe Foschi
- Medicina Interna Faenza, Dipartimento Emergenza, Medicina Interna e Cardioloa IRCCS-Istituto Scientifico Romagnolo per lo Studio dei Tumori “Dino Amadori” Meldola, AUSL Romagna, Meldola, Italy
| | - Gianluca Svegliati-Baroni
- Liver Injury and Transplant Unit and Obesity Center, Polytechnic University of Marche, Ancona, Italy
| | - Angelo Sangiovanni
- Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy
| | - Claudia Campani
- Department of Experimental and Clinical Medicine, Internal Medicine and Hepatology Unit, University of Firenze, Florence, Italy
| | - Giovanni Raimondo
- Department of Clinical and Experimental Medicine, Division of Medicine and Hepatology, University of Messina, Messina, Italy
| | - Gianpaolo Vidili
- Department of Medicine, Surgery and Pharmacy, AOU Sassari, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS and Università Cattolica del Sacro Cuore, Rome, Italy
| | - Ciro Celsa
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy
| | | | - Edoardo G. Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
- Gastroenterology Unit, IRCCS Ospedale San Martino, Genoa, Italy
| | - Rodolfo Sacco
- Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, Foggia, Italy
| | | | - Francesco Azzaroli
- Gastroenterology Unit, Department of Surgical and Medical Sciences, IRCCS Azienda Ospedaliero, Universitaria di Bologna, Bologna, Italy
| | - Donatella Magalotti
- Division of Internal Medicine, Neurovascular and Hepatometabolic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Filomena Morisco
- Department of Clinical Medicine and Surgery, Departmental Program “Diseases of the Liver and Biliary System”, University of Napoli “Federico II”, Naples, Italy
| | | | - Gerardo Nardone
- Department of Clinical Medicine and Surgery, Hepato-Gastroenterology Unit, University of Napoli “Federico II”, Naples, Italy
| | - Alessandro Vitale
- Department of Surgical, Oncological, and Gastroenterological Sciences, Hepatobiliary Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
| | - Franco Trevisani
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
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Bitzer M, Groß S, Albert J, Boda-Heggemann J, Brunner T, Caspari R, De Toni E, Dombrowski F, Evert M, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Kautz A, Krug D, Fougère CL, Lang H, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Ockenga J, Oldhafer K, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ritterbusch U, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schuler A, Seehofer D, Sinn M, Stengel A, Stoll C, Tannapfel A, Taubert A, Tholen R, Trojan J, van Thiel I, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wildner D, Wörns MA, Galle P, Malek N. S3-Leitlinie Diagnostik und Therapie biliärer Karzinome – Langversion. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:e92-e156. [PMID: 37040776 DOI: 10.1055/a-2026-1240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/13/2023]
Affiliation(s)
- Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | | | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | | | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschrirugie, Eberhard-Karls Universität, Tübingen
| | | | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Klinik für Innere Medizin, Gesundheit Nord, Klinikverbund Bremen
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | | | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | | | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Reina Tholen
- Deutscher Bundesverband für Physiotherapie (ZVK) e. V
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Arndt Vogel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
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19
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Etiologic fractions in patients of hepatocellular carcinoma in India with and without a background of cirrhosis: a multi-centric study. Hepatol Int 2023; 17:745-752. [PMID: 36940070 DOI: 10.1007/s12072-023-10498-w] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 02/04/2023] [Indexed: 03/21/2023]
Abstract
BACKGROUND Hepatocellular cancer (HCC) typically arises in the background of cirrhosis. The epidemiology of HCC has changed in recent years due to availability of newer antivirals, changing life-styles and greater possibility for early detection. We undertook a multicentric national sentinel surveillance for liver cirrhosis and HCC to assess the attributable risk factors for the development of HCC, both with and without a background of cirrhosis. METHODS Data from January 2017 till August 2022 from hospital-based records of eleven participating centers were included. Diagnosed cases of cirrhosis [radiological (multiphase and/or histopathological] and HCC [as per AASLD 2018] were included. History of significant alcohol intake was elicited by AUDIT-C questionnaire. RESULTS Altogether 5798 enrolled patients were assessed, of which 2664 patients had HCC. The mean age was 58.2 ± 11.7 years and 84.3% (n = 2247) were males. Diabetes was found in over a third of those with HCC (n = 1032;39.5%). The most common etiology of HCC was NAFLD (n = 927;35.5%) followed by viral hepatitis B and C and harmful levels of alcohol. Among those with HCC, 27.9% (n = 744) had no cirrhosis. Higher proportion of cirrhotic HCC patients had alcohol as an etiological factor as compared to non-cirrhotic (17.5 vs. 4.7%, p ≤ 0.001). NAFLD was an etiological factor for a higher proportion of non-cirrhotic HCC patients as compared to cirrhotic HCC (48.2 vs. 30.6%, p ≤0.001). Diabetics more commonly had non-cirrhotic HCC (50.5 vs. 35.2%). The following factors were associated with an occurrence of cirrhotic HCC: male gender (OR 1.372 and 95% CI 1.070-1.759), age above 60 years (OR 1.409 and 95% CI 1.176-1.689), HBV (OR 1.164 and 95% CI 0.928-1.460), HCV (OR 1.228 and 95 CI 0.964-1.565) and harmful consumption of alcohol (OR 3.472 and 95% CI 2.388-5.047). The adjusted odds of non-cirrhotic patients having NAFLD was 1.553 (95% CI 1.290-1.869). CONCLUSION This large multi-centric study demonstrates that NAFLD is the most important risk factor for development of both cirrhotic and non-cirrhotic HCC in India and has overtaken viral hepatitis. Awareness campaigns and large-scale screening are required to reduce the high burden of NAFLD-related HCC in India.
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Preoperative Predictors of Early Recurrence After Liver Resection for Multifocal Hepatocellular Carcinoma. J Gastrointest Surg 2023:10.1007/s11605-023-05592-1. [PMID: 36857014 DOI: 10.1007/s11605-023-05592-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 01/07/2023] [Indexed: 03/02/2023]
Abstract
BACKGROUND Liver transplantation remains the optimal treatment for multifocal hepatocellular carcinoma (HCC). However, due to resource constrains, other therapeutic modalities such as liver resection (LR), are frequently utilized. LR, however, has to be balanced against potential morbidity and mortality along with the risks of early recurrence leading to futile surgery. In this study, we evaluated preoperative factors, including inflammatory indices, in predicting early (< 1 year) recurrence in patients who underwent LR for multifocal HCC. METHODS This was a post hoc analysis of 250 consecutive patients with multifocal HCC who underwent LR. RESULTS After exclusion of 10 patients with 30-day/in-hospital mortality, 240 were included of which 134 (55.8%) developed early recurrence. Hepatitis B/C aetiology, 3/ > more hepatic nodules and elevated alpha-fetoprotein (AFP) ≥ 200 ng/ml were significant independent preoperative predictors of early recurrence. The early recurrence rate was 72.1% when 2 out of 3 significant predictive factors were present. The conglomerate of all 3 factors predicted early recurrence of 100% with a statistically significant association between number of predictive factors and early recurrence (p < 0.001). CONCLUSION Better patient selection via the use of preoperative predictive factors of early recurrence such as hepatitis B/C aetiology, ≥ 3 nodules and elevated AFP ≥ 200 ng/ml may assist in identifying patients in whom LR is deemed futile and improve resource allocation.
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21
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Pal Chaudhary S, Reyes S, Chase ML, Govindan A, Zhao L, Luther J, Bhan I, Bethea E, Franses JW, Paige Walsh E, Anne Dageford L, Kimura S, Elias N, Yeh H, Markman J, Bozorgzadeh A, Tanabe K, Ferrone C, Zhu AX, Andersson K, Thiim M, Antonio Catalano O, Kambadakone A, Vagefi PA, Qadan M, Pratt D, Hashemi N, Corey KE, Misdraji J, Goyal L, Clark JW. Resection of NAFLD/NASH-related Hepatocellular Carcinoma (HCC): Clinical Features and Outcomes Compared with HCC Due to Other Etiologies. Oncologist 2023; 28:341-350. [PMID: 36763374 PMCID: PMC10078904 DOI: 10.1093/oncolo/oyac251] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Accepted: 10/19/2022] [Indexed: 02/11/2023] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are the leading causes of hepatocellular carcinoma (HCC) worldwide. Limited data exist on surgical outcomes for NAFLD/NASH-related HCC compared with other HCC etiologies. We evaluated differences in clinicopathological characteristics and outcomes of patients undergoing surgical resection for NAFLD/NASH-associated HCC compared with other HCC etiologies. METHODS Demographic, clinicopathological features, and survival outcomes of patients with surgically resected HCC were collected. NAFLD activity score (NAS) and fibrosis score were assessed by focused pathologic review in a subset of patients. RESULTS Among 492 patients screened, 260 met eligibility (NAFLD/NASH [n = 110], and other etiologies [n = 150]). Median age at diagnosis was higher in the NAFLD/NASH HCC cohort compared with the other etiologies cohort (66.7 vs. 63.4 years, respectively, P = .005), with an increased percentage of female patients (36% vs. 18%, P = .001). NAFLD/NASH-related tumors were more commonly >5 cm (66.0% vs. 45%, P = .001). There were no significant differences in rates of lymphovascular or perineural invasion, histologic grade, or serum AFP levels. The NAFLD/NASH cohort had lower rates of background liver fibrosis, lower AST and ALT levels, and higher platelet counts (P < .01 for all). Median overall survival (OS) was numerically shorter in NAFLD/NASH vs other etiology groups, however, not statistically significant. CONCLUSIONS Patients with NAFLD/NASH-related HCC more commonly lacked liver fibrosis and presented with larger HCCs compared with patients with HCC from other etiologies. No differences were seen in rates of other high-risk features or survival. With the caveat of sample size and retrospective analysis, this supports a similar decision-making approach regarding surgical resection for NAFLD/NASH and other etiology-related HCCs.
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Affiliation(s)
- Surendra Pal Chaudhary
- Division of Oncology, Mass General Cancer Center and Harvard Medical School, Boston, MA, USA
| | | | | | | | - Lei Zhao
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Jay Luther
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Irun Bhan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Emily Bethea
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Joseph W Franses
- Division of Oncology, Mass General Cancer Center and Harvard Medical School, Boston, MA, USA
| | - Elizabeth Paige Walsh
- Division of Oncology, Mass General Cancer Center and Harvard Medical School, Boston, MA, USA
| | - Leigh Anne Dageford
- Transplantation Unit, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Shoko Kimura
- Transplantation Unit, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Nahel Elias
- Transplantation Unit, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Heidi Yeh
- Transplantation Unit, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - James Markman
- Transplantation Unit, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Adel Bozorgzadeh
- Transplantation Unit, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Kenneth Tanabe
- Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Cristina Ferrone
- Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Andrew X Zhu
- Jiahui Health, Jiahui International Cancer Center, Shanghai, People's Republic of China
| | - Karin Andersson
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Michael Thiim
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Onofrio Antonio Catalano
- Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Avinash Kambadakone
- Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Parsia A Vagefi
- Division of Surgical Transplantation, University of Texas Southwestern, Dallas, TX, USA
| | - Motaz Qadan
- Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Daniel Pratt
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Nikroo Hashemi
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Kathleen E Corey
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Joseph Misdraji
- Department of Pathology, Yale New Haven Hospital, Yale University, New Haven, CT, USA
| | - Lipika Goyal
- Division of Oncology, Mass General Cancer Center and Harvard Medical School, Boston, MA, USA
| | - Jeffrey W Clark
- Division of Oncology, Mass General Cancer Center and Harvard Medical School, Boston, MA, USA
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22
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Li Y, Zhao JF, Zhang J, Zhan GH, Li YK, Huang JT, Huang X, Xiang BD. Inflammation and Fibrosis in Patients with Non-Cirrhotic Hepatitis B Virus-Associated Hepatocellular Carcinoma: Impact on Prognosis after Hepatectomy and Mechanisms Involved. Curr Oncol 2022; 30:196-218. [PMID: 36661665 PMCID: PMC9858133 DOI: 10.3390/curroncol30010016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 12/13/2022] [Accepted: 12/20/2022] [Indexed: 12/24/2022] Open
Abstract
Background: We investigated whether the degree of inflammation and fibrosis in para-carcinoma tissue can predict prognosis of patients with non-cirrhotic hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) after hepatectomy. We also explored the mechanisms through which inflammation and fibrosis might affect prognosis. Methods: Clinicopathological data were retrospectively analyzed from 293 patients with non-cirrhotic HBV-associated HCC who were treated at our institution by curative resection from 2012 to 2017. Based on the Scheuer score system, patients were classified into those showing mild or moderate-to-severe inflammation and fibrosis. Rates of overall and recurrence-free survival were compared between the groups using Kaplan-Meier curves, and survival predictors were identified using Cox regression. Using tumor and para-tumor tissues from independent samples of patients with non-cirrhotic HBV-associated HCC who were treated at our institution by curative resection from 2018 to 2019, we performed next-generation sequencing and time-of-flight cytometry (CyTOF) to examine the influence of inflammation and fibrosis on gene expression and immune cell infiltration. Results: In the analysis of the 293 patients, those with mild inflammation and fibrosis showed significantly better overall and recurrence-free survival than those with moderate-to-severe inflammation and fibrosis. Multivariate Cox regression confirmed that moderate-to-severe inflammation and fibrosis were independent risk factors for worse survival. RNA sequencing and CyTOF showed that more severe inflammation and fibrosis were associated with stronger invasion and migration by hepatocytes. In cancerous tissues, the biological processes of cell proliferation were upregulated, the signaling pathways promoting tumor growth were activated, the proportion of Th17 cells promoting tumor progression was increased, and CD8+ T cells expressed higher levels of PD-L1. In para-cancerous tissues, biological processes of immune response and cell chemotaxis were downregulated, and the proportion of tumor-killing immune cells was decreased. Conclusion: Worse inflammation and fibrosis in non-cirrhotic HBV-associated HCC is associated with worse prognosis, which may reflect more aggressive tumor behavior and an immunosuppressed, pro-metastatic tumor microenvironment.
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Affiliation(s)
- Yan Li
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Jing-Fei Zhao
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Jie Zhang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Guo-Hua Zhan
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Yuan-Kuan Li
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Jun-Tao Huang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Xi Huang
- The First Clinical School of Guangxi Medical University, Nanning 530021, China
| | - Bang-De Xiang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, China
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23
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Is Fasting Good When One Is at Risk of Liver Cancer? Cancers (Basel) 2022; 14:cancers14205084. [PMID: 36291868 PMCID: PMC9600146 DOI: 10.3390/cancers14205084] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 10/13/2022] [Accepted: 10/14/2022] [Indexed: 11/17/2022] Open
Abstract
Hepatocellular carcinoma (HCC), one of the leading causes of cancer-related deaths worldwide, is a multistep process that usually develops in the background of cirrhosis, but also in a non-cirrhotic state in patients with non-alcoholic fatty liver disease (NAFLD) or viral hepatis. Emerging evidence suggests that intermittent fasting can reduce the risk of cancer development and could improve response and tolerance to treatment through the metabolic and hormonal adaptations induced by the low energy availability that finally impairs cancer cells’ adaptability, survival and growth. The current review will outline the beneficial effects of fasting in NAFLD/NASH patients and the possible mechanisms that can prevent HCC development, including circadian clock re-synchronization, with a special focus on the possibility of applying this dietary intervention to cirrhotic patients.
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24
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MicroRNA-20a-5p regulates the epithelial-mesenchymal transition of human hepatocellular carcinoma by targeting RUNX3. Chin Med J (Engl) 2022; 135:2089-2097. [PMID: 35143426 PMCID: PMC9746768 DOI: 10.1097/cm9.0000000000001975] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND MicroRNA-20a (miR-20a) is dysregulated in many types of malignancies, including human hepatocellular carcinoma (HCC), but its expression level and functional significance in HCC are still disputed. We aimed to study the role of miR-20a-5p in HCC and its downstream molecular mechanisms. METHODS We used real-time polymerase chain reaction to detect the expression of miR-20a-5p and runt-related transcription factor 3 ( RUNX3 ) in HCC and paraneoplastic tissue, transfected Huh7 and highly metastatic human hepatocellular carcinoma (MHCC97H) cells. A live cell workstation was used to observe the proliferation and migration of transfected cells. The invasiveness of transfected cells was verified by Transwell assay. Cell apoptosis was detected by flow cytometry. The expression levels of proteins after transfection were measured using simple western immunoblot measurements. Gene expression profiles between HCC and normal samples were obtained from The Cancer Genome Atlas. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were processed by the database for annotation, visualization and integrated discovery. Potential target genes of miR-20a-5p were predicted to further investigate how miR-20a-5p regulates epithelial-mesenchymal transition (EMT) in HCC. RESULTS MiR-20a-5p was significantly highly expressed in HCC tissues, and overexpression of miR-20a-5p significantly promoted HCC cell proliferation, migration, and invasion and inhibited apoptosis in vitro. The protein expression of E-cadherin was decreased and that of vimentin was increased after overexpression of miR-20a-5p in HCC cells. We discovered the intersection of genes from miRDB, miR TarBase, and TargetScan, obtained 397 target genes and finally focused on RUNX3. RUNX3 was not only reduced in HCC specimens but also drastically reduced in HCC cells overexpressing miR-20a-5p. RUNX3 expression decreased with elevated miR-20a-5p, which activated downstream EMT signaling and promoted cell proliferation, migration, and invasion. CONCLUSIONS Since RUNX3 is involved in EMT in HCC, as proven by previous research, our findings provide further evidence for a novel regulatory pathway comprising the miR-20a/RUNX3/EMT axis that upregulates EMT signaling and enhances the migration of HCC cells.
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25
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Cisneros-Garza LE, González-Huezo MS, Moctezuma-Velázquez C, Ladrón de Guevara-Cetina L, Vilatobá M, García-Juárez I, Alvarado-Reyes R, Álvarez-Treviño GA, Allende-Pérez S, Bornstein-Quevedo L, Calderillo-Ruiz G, Carrillo-Martínez MA, Castillo-Barradas M, Cerda-Reyes E, Félix-Leyva JA, Gabutti-Thomas JA, Guerrero-Ixtlahuac J, Higuera-de la Tijera F, Huitzil-Melendez D, Kimura-Hayama E, López-Hernández PA, Malé-Velázquez R, Méndez-Sánchez N, Morales-Ruiz MA, Ruíz-García E, Sánchez-Ávila JF, Torrecillas-Torres L. The second Mexican consensus on hepatocellular carcinoma. Part II: Treatment. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2022; 87:362-379. [PMID: 35778341 DOI: 10.1016/j.rgmx.2022.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 01/20/2022] [Indexed: 01/03/2025]
Abstract
Hepatocellular carcinoma (HCC) is more frequently manifesting as one of the main complications of cirrhosis of the liver, its principal risk factor. There have been modifications in its incidence over the past decade, related to an epidemiologic transition in the etiology of cirrhosis, with a decrease in the prevalence of hepatitis C and an increase in nonalcoholic fatty liver disease (NAFLD) as a cause, as well as the development of HCC in the non-cirrhotic liver due to NAFLD. Genetic markers associated with the disease have been identified, and surveillance and diagnosis have improved. Regarding treatment, surgical techniques, in both resection and transplantation, have advanced and radiologic techniques, at the curative stage of the disease, have enhanced survival in those patients. And finally, there have been radical changes in the systemic approach, with much more optimistic expectations, when compared with the options available a decade ago. Therefore, the Asociación Mexicana de Hepatología decided to carry out the Second Mexican Consensus on Hepatocellular Carcinoma, which is an updated review of the available national and international evidence on the epidemiology, risk factors, surveillance, diagnosis, and treatment of the disease, to offer the Mexican physician current information on the different topics regarding hepatocellular carcinoma. In this second part of the document, the topics related to the treatment of HCC are presented.
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Affiliation(s)
- L E Cisneros-Garza
- Hospital Christus Muguerza Alta Especialidad, Monterrey, Nuevo León, Mexico.
| | | | | | | | - M Vilatobá
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, CDMX, Mexico
| | - I García-Juárez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, CDMX, Mexico
| | | | | | | | - L Bornstein-Quevedo
- InmunoQ, Laboratorio de Patología, Inmunohistoquímica y Biología Molecular, CDMX, Mexico
| | | | | | | | | | | | - J A Gabutti-Thomas
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, CDMX, Mexico
| | | | | | - D Huitzil-Melendez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, CDMX, Mexico
| | | | | | - R Malé-Velázquez
- Instituto de Salud Digestiva y Hepática SA de CV, Guadalajara, Jalisco, Mexico
| | | | - M A Morales-Ruiz
- Centro Oncológico Estatal Issemym, Toluca, Estado de México, Mexico
| | | | - J F Sánchez-Ávila
- Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey, Nuevo León, Mexico
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26
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Cisneros-Garza L, González-Huezo M, Moctezuma-Velázquez C, Ladrón de Guevara-Cetina L, Vilatobá M, García-Juárez I, Alvarado-Reyes R, Álvarez-Treviño G, Allende-Pérez S, Bornstein-Quevedo L, Calderillo-Ruiz G, Carrillo-Martínez M, Castillo-Barradas M, Cerda-Reyes E, Félix-Leyva J, Gabutti-Thomas J, Guerrero-Ixtlahuac J, Higuera-de la Tijera F, Huitzil-Melendez D, Kimura-Hayama E, López-Hernández P, Malé-Velázquez R, Méndez-Sánchez N, Morales-Ruiz M, Ruíz-García E, Sánchez-Ávila J, Torrecillas-Torres L. The second Mexican consensus on hepatocellular carcinoma. Part II: Treatment. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2022; 87:362-379. [DOI: 10.1016/j.rgmxen.2022.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 01/20/2022] [Indexed: 10/25/2022] Open
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27
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Bredt LC, Felisberto IBG, Felisberto DEG. Is there a role for liver transplantation in the treatment of hepatocellular carcinoma in non-cirrhotic liver? World J Meta-Anal 2022; 10:46-51. [DOI: 10.13105/wjma.v10.i2.46] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 03/21/2022] [Accepted: 04/28/2022] [Indexed: 02/06/2023] Open
Abstract
Whether liver transplantation (LT) plays a role in the treatment of patients with hepatocellular carcinoma (HCC) in non-cirrhotic liver (NCL) is a matter of debate. The recommendations for LT in this setting are extremely fragile and less well-defined than for cirrhosis-associated HCC. All reports of LT for NCL-HCC revealed that long-term outcomes of these patients are poor, and these dismal figures are justified by the advanced tumor stage at the time of LT, suggesting the presence of systemic micrometastatic disease. The decision-making regarding LT for NCL-HCC is difficult, since specific selection criteria are scarce, and basically the potential candidates are those with unresectable only-liver tumor at admission, or unresectable intrahepatic recurrence post-resection. Besides the surgical aspects regarding the tumor resectability, other phenotypic and genetic characteristics of the tumor should be considered for the indication of LT in this scenario. The present minireview aims to discuss and analyze the last series of LT for NCL-HCC, in order to help clinicians in the decision-making process regarding the role of LT in NCL-HCC treatment.
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Affiliation(s)
- Luis Cesar Bredt
- Surgical Oncology and Hepatobiliary Surgery, Unioeste University, Cascavel 85819-110, Paraná, Brazil
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28
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Yin H, Miao Z, Wang L, Su B, Liu C, Jin Y, Wu B, Han H, Yuan X. Fusobacterium nucleatum promotes liver metastasis in colorectal cancer by regulating the hepatic immune niche and altering gut microbiota. Aging (Albany NY) 2022; 14:1941-1958. [PMID: 35212644 PMCID: PMC8908934 DOI: 10.18632/aging.203914] [Citation(s) in RCA: 54] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 12/11/2021] [Indexed: 11/25/2022]
Abstract
Liver metastasis is the major cause of death in colorectal cancer (CRC) patients. Nevertheless, the underlying mechanisms remain unknown. Gut microbiota intricately affect the initiation and progression of CRC by instigating immune response through the secretion of pro-inflammatory cytokines. In this study, we investigated the contribution of Fusobacterium nucleatum (F.nucleatum) to the microbiota-liver axis of CRC in mice, focusing on the correlation between liver immunity and gut microbiota alterations. When F. nucleatum was orally administered to mice, CRC liver metastasis was evidently exaggerated and accompanied by noticeable deleterious effects on body weight, cecum weight, and overall survival time. Further evaluation of the immune response and cytokine profiles revealed a substantial increase in the levels of pro-inflammatory cytokines such as IL6, IL12, IL9, IL17A, CXCL1, MCP-1, TNF-α, and IFN-γ in the plasma of mice treated with F. nucleatum as compared to that in the untreated control mice. Besides, hepatic immune response was also modulated by recruitment of myeloid-derived suppressor cells, reduction in the infiltration of natural killer (NK) and T helper-17 (Th17) cells, as well as increase in regulatory T cell accumulation in the liver. Additionally, sustained F. nucleatum exposure abridged the murine gut microbiota diversity, inducing an imbalanced and restructured intestinal microflora. In particular, the abundance of CRC-promoting bacteria such as Enterococcus and Escherichia/Shigella was evidently elevated post F. nucleatum treatment. Thus, our findings suggest that F. nucleatum might be an important factor involved in promoting CRC liver metastasis by triggering of liver immunity through the regulation of gut microbiota structure and composition.
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Affiliation(s)
- Han Yin
- Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Zhuangzhuang Miao
- Department of Neurosurgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Lu Wang
- Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Beibei Su
- Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Chaofan Liu
- Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Yu Jin
- Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Bili Wu
- Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Hu Han
- Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Xianglin Yuan
- Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
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29
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Jain A, Mazer B, Deng Y, Ciarleglio M, Jain D, Taddei T, Zhang X. Hepatocellular Carcinoma: Does the Background Liver With or Without Cirrhosis Matter? Am J Clin Pathol 2022; 157:305-313. [PMID: 34542582 DOI: 10.1093/ajcp/aqab125] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Accepted: 06/24/2021] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVES The pathologic differences between hepatocellular carcinoma (HCC) arising in noncirrhotic and cirrhotic livers have not been well studied. METHODS We performed a retrospective analysis of 378 HCC cases (95 in noncirrhotic, 283 in cirrhotic livers) from pathology archives (2010-2017). RESULTS Patients without cirrhosis were more likely to have hepatitis B (13.68% vs 2.83%, P < .001) or no known liver disease (30.53% vs 4.24%, P < .001), while hepatitis C was more common in patients with cirrhosis (65.72% vs 30.53%, P < .001). HCCs in noncirrhotic livers were larger in size (P < .001); were more likely to have a macrotrabecular histologic pattern (13.68% vs 4.95%, P < .01); were more likely to have fibrolamellar (3.16% vs 0%, P = .02), macrotrabecular-massive (13.68% vs 6.01%, P = .03), and clear cell (16.84% vs 6.71%, P < .01) subtypes; have a higher histologic grade (P < .01); be anaplastic tumor cells (P < .001); have a higher rate of vascular invasion (P < .01); and have a higher tumor stage (P = .04). CONCLUSIONS The findings indicate that HCCs in noncirrhotic livers demonstrate a larger tumor size; have a more macrotrabecular histologic pattern; have fibrolamellar, macrotrabecular-massive, and clear cell subtypes; have a higher tumor grade and stage; have a higher rate of vascular invasion; and have more anaplastic tumor cells compared with cirrhotic livers. Further studies to explore different pathways that promote oncogenesis in noncirrhotic livers are needed to better understand the pathogenesis of HCC.
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Affiliation(s)
| | | | - Yanhong Deng
- Yale Center for Analytical Sciences, New Haven, CT, USA
| | | | | | - Tamar Taddei
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
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30
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Sabrina V, Michael B, Jörg A, Peter B, Wolf B, Susanne B, Thomas B, Frank D, Matthias E, Markus F, Christian LF, Paul F, Andreas G, Eleni G, Martin G, Elke H, Thomas H, Ralf-Thorsten H, Wolf-Peter H, Peter H, Achim K, Gabi K, Jürgen K, David K, Frank L, Hauke L, Thomas L, Philipp L, Andreas M, Alexander M, Oliver M, Silvio N, Huu Phuc N, Johann O, Karl-Jürgen O, Philipp P, Kerstin P, Philippe P, Thorsten P, Mathias P, Ruben P, Jürgen P, Jutta R, Peter R, Johanna R, Ulrike R, Elke R, Barbara S, Peter S, Irene S, Andreas S, Dietrich VS, Daniel S, Marianne S, Alexander S, Andreas S, Nadine S, Christian S, Andrea T, Anne T, Jörg T, Ingo VT, Reina T, Arndt V, Thomas V, Hilke V, Frank W, Oliver W, Heiner W, Henning W, Dane W, Christian W, Marcus-Alexander W, Peter G, Nisar M. S3-Leitlinie: Diagnostik und Therapie des hepatozellulären Karzinoms. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e56-e130. [PMID: 35042248 DOI: 10.1055/a-1589-7568] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Voesch Sabrina
- Medizinische Klinik I, Universitätsklinikum Tübingen, Tübingen
| | - Bitzer Michael
- Medizinische Klinik I, Universitätsklinikum Tübingen, Tübingen
| | - Albert Jörg
- Abteilung für Gastroenterologie, Hepatologie und Endokrinologie, Stuttgart
| | | | - Bechstein Wolf
- Klinik für Allgemein-, Viszeral-, Transplantations- und Thoraxchirurgie, Universitätsklinikum Frankfurt, Frankfurt am Main
| | | | - Brunner Thomas
- Klinik für Strahlentherapie, Universitätsklinikum Magdeburg A. ö. R., Magdeburg
| | - Dombrowski Frank
- Institut für Pathologie, Universitätsmedizin Greifswald, Greifswald
| | | | - Follmann Markus
- Office des Leitlinienprogrammes Onkologie, c/o Deutsche Krebsgesellschaft e.V. Berlin
| | | | | | - Geier Andreas
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg
| | - Gkika Eleni
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg, Freiburg
| | | | - Hammes Elke
- Lebertransplantierte Deutschland e. V., Ansbach
| | - Helmberger Thomas
- Institut für Radiologie, Neuroradiologie und minimal-invasive Therapie, München Klinik Bogenhausen, München
| | | | - Hofmann Wolf-Peter
- Gastroenterologie am Bayerischen Platz, medizinisches Versorgungszentrum, Berlin
| | | | | | - Knötgen Gabi
- Konferenz onkologischer Kranken- und Kinderkrankenpflege, Hamburg
| | - Körber Jürgen
- Klinik Nahetal, Fachklinik für onkologische Rehabilitation und Anschlussrehabilitation, (AHB), Bad Kreuznach
| | - Krug David
- Klinik für Strahlentherapie, Universitätsklinikum Schleswig-Holstein, Kiel
| | | | - Lang Hauke
- Klinik für Allgemein-, Viszeral und Transplantationschirurgie, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz
| | - Langer Thomas
- Office des Leitlinienprogrammes Onkologie, c/o Deutsche Krebsgesellschaft e.V. Berlin
| | - Lenz Philipp
- Universitätsklinikum Münster, Zentrale Einrichtung Palliativmedizin, Münster
| | - Mahnken Andreas
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Gießen und Marburg GmbH, Marburg
| | - Meining Alexander
- Medizinische Klinik und Poliklinik II des Universitätsklinikums Würzburg, Würzburg
| | - Micke Oliver
- Klinik für Strahlentherapie und Radioonkologie, Franziskus Hospital Bielefeld, Bielefeld
| | - Nadalin Silvio
- Universitätsklinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Tübingen, Tübingen
| | | | | | - Oldhafer Karl-Jürgen
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Semmelweis Universität, Asklepios Campus Hamburg, Hamburg
| | - Paprottka Philipp
- Abteilung für interventionelle Radiologie, Klinikum rechts der Isar der Technischen Universität München, München
| | - Paradies Kerstin
- Konferenz onkologischer Kranken- und Kinderkrankenpflege, Hamburg
| | - Pereira Philippe
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, Klinikum am Gesundbrunnen, SLK-Kliniken Heilbronn GmbH, Heilbronn
| | - Persigehl Thorsten
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln, Köln
| | | | | | - Pohl Jürgen
- Interventionelles Endoskopiezentrum und Schwerpunkt Gastrointestinale Onkologie, Asklepios Klinik Altona, Hamburg
| | - Riemer Jutta
- Lebertransplantierte Deutschland e. V., Bretzfeld
| | - Reimer Peter
- Institut für diagnostische und interventionelle Radiologie, Städtisches Klinikum Karlsruhe gGmbH, Karlsruhe
| | - Ringwald Johanna
- Psychosomatische Medizin und Psychotherapie, Universitätsklinikum Tübingen, Tübingen
| | | | - Roeb Elke
- Medizinische Klinik II, Universitätsklinikum Gießen und Marburg GmbH, Gießen
| | - Schellhaas Barbara
- Medizinische Klinik I, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen
| | - Schirmacher Peter
- Pathologisches Institut, Universitätsklinikum Heidelberg, Heidelberg
| | - Schmid Irene
- Zentrum Pädiatrische Hämatologie und Onkologie, Dr. von Haunersches Kinderspital, Klinikum der Universität München, München
| | | | | | - Seehofer Daniel
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig
| | - Sinn Marianne
- Medizinische Klinik II, Universitätsklinikum Hamburg-Eppendorf, Hamburg
| | | | - Stengel Andreas
- Psychosomatische Medizin und Psychotherapie, Universitätsklinikum Tübingen, Tübingen
| | | | | | - Tannapfel Andrea
- Institut für Pathologie der Ruhr-Universität Bochum am Berufsgenossenschaftlichen Universitätsklinikum Bergmannsheil, Bochum
| | - Taubert Anne
- Kliniksozialdienst, Universitätsklinikum Heidelberg, Bochum
| | - Trojan Jörg
- Medizinische Klinik I, Universitätsklinikum Frankfurt, Frankfurt am Main
| | | | - Tholen Reina
- Deutscher Verband für Physiotherapie e. V., Köln
| | - Vogel Arndt
- Klinik für Gastroenterologie, Hepatologie, Endokrinologie der Medizinischen Hochschule Hannover, Hannover
| | - Vogl Thomas
- Universitätsklinikum Frankfurt, Institut für Diagnostische und Interventionelle Radiologie, Frankfurt
| | - Vorwerk Hilke
- Klinik für Strahlentherapie, Universitätsklinikum Gießen und Marburg GmbH, Marburg
| | - Wacker Frank
- Institut für Diagnostische und Interventionelle Radiologie der Medizinischen Hochschule Hannover, Hannover
| | - Waidmann Oliver
- Medizinische Klinik I, Universitätsklinikum Frankfurt, Frankfurt am Main
| | - Wedemeyer Heiner
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie Medizinische Hochschule Hannover, Hannover
| | - Wege Henning
- I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg
| | - Wildner Dane
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Lauf an der Pegnitz
| | | | | | - Galle Peter
- I. Medizinische Klinik und Poliklinik, Universitätsklinikum Mainz, Mainz
| | - Malek Nisar
- Medizinische Klinik I, Universitätsklinikum Tübingen, Tübingen
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Kim JM, Rhu J, Ha SY, Choi GS, Kwon CHD, Joh JW. Hepatectomy outcomes in patients with hepatitis C virus-related hepatocellular carcinoma with or without cirrhosis. Ann Surg Treat Res 2022; 102:1-9. [PMID: 35071114 PMCID: PMC8753383 DOI: 10.4174/astr.2022.102.1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 11/07/2021] [Accepted: 12/03/2021] [Indexed: 01/27/2023] Open
Abstract
Purpose Hepatocellular carcinoma (HCC) is rare in HCV patients without cirrhosis, and little is known about the postoperative results of these patients. The present study compares the outcomes of cirrhotic and non-cirrhotic groups after liver resection (LR) in solitary HCV-related HCC patients and identifies risk factors for prognosis according to the presence or absence of cirrhosis in these patients. Methods Two hundred and 7 adult hepatectomy patients with treatment-naïve solitary HCV-related HCC were identified prospectively at our institution between July 2005 and May 2019. Results The non-cirrhotic group had better liver function than the cirrhotic group based on platelet count, liver function tests, liver stiffness measurement, and indocyanine green retention rate at 15 minutes but were older than the cirrhotic group. Consistently, noninvasive markers in the cirrhotic group were significantly higher than in the non-cirrhotic group. The cumulative disease-free survival and overall survival in the non-cirrhotic group were significantly higher than in the cirrhotic group. HCC recurrence was related to major LR and α-FP of >40 ng/mL and death was related to long hospitalization and α-FP of >40 ng/mL in multivariate analysis. Noninvasive markers and the presence of cirrhosis were not related to HCC recurrence or death in multivariate analyses. Conclusion The cirrhotic group showed poor prognosis due to poor liver function after LR compared to the non-cirrhotic group, but this was not sustained in multivariate analysis. The factors influencing HCC recurrence and death were different in the cirrhotic and non-cirrhotic groups.
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Affiliation(s)
- Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sang Yun Ha
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Gyu-Seong Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Choon Hyuck David Kwon
- Department of Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Jae-Won Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Musunuri B, Shetty S, Bhat G, Udupa K, Pai A. Profile of patients with hepatocellular carcinoma: An experience from a tertiary care center in India. Indian J Gastroenterol 2022; 41:127-134. [PMID: 35226292 PMCID: PMC9108108 DOI: 10.1007/s12664-021-01209-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 06/07/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND The prevalence of hepatocellular carcinoma (HCC) is increasing worldwide and it is now the third most common cause of cancer-related death. HCC is becoming a major health burden with steadily increasing incidence globally. METHODS This is an observational study over a 3-year period in a tertiary care center in India. Three hundred and thirty-nine patients diagnosed to have HCC were included in this study. Patients' clinical, etiological, radiological and cytohistological data and therapy offered were recorded and analyzed. RESULTS Cirrhosis of the liver was seen in 73.2% of the patients. 16.8% of patients were asymptomatic at the time of presentation. Ascites (57.2%) and jaundice (22.4%) were the most common signs of hepatic decompensation. The most common etiology of HCC was cryptogenic/non-alcoholic fatty liver disease (NAFLD) in 51% of the patients, while hepatitis B and C were seen in 17.4% and 5.8% of the patients, respectively. Advanced and end-stage disease with Barcelona Clinic Liver Cancer (BCLC) stages C and D were seen in 62.4% of patients. 56.6% had Albumin-bilirubin (ALBI) score of 2, while 62.8% had Okuda stage II disease. High alpha-fetoprotein (AFP) levels (>400 ng/mL) were seen in 48.9% of patients. Macrovascular invasion and metastases were seen in 45.9% and 22.2% of the patients, respectively. 17.6% of patients had evidence of tumor thrombus. 14.5% of biopsy specimens showed associated steatosis/steatohepatitis along with confirmation of HCC. Only 26.6% of the cirrhotic HCC patients were diagnosed during surveillance. CONCLUSIONS HCC due to unknown cause/NAFLD appears to be overtaking hepatitis B as the commonest cause for HCC. Despite the advances in diagnostic methods and surveillance, most cases of HCC tend to be diagnosed at advanced stages.
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Affiliation(s)
- Balaji Musunuri
- Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 576 104, India
| | - Shiran Shetty
- Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 576 104, India
| | - Ganesh Bhat
- Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 576 104, India
| | - Karthik Udupa
- Department of Medical Oncology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 576 104, India
| | - Ananth Pai
- Department of Medical Oncology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 576 104, India
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Ezzat R, Eltabbakh M, El Kassas M. Unique situation of hepatocellular carcinoma in Egypt: A review of epidemiology and control measures. World J Gastrointest Oncol 2021; 13:1919-1938. [PMID: 35070033 PMCID: PMC8713321 DOI: 10.4251/wjgo.v13.i12.1919] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 04/17/2021] [Accepted: 10/18/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common primary malignancy worldwide, and the third most common cause of death among cancers worldwide. HCC occurs in several pre-existing conditions, including hepatitis C, hepatitis B virus, and non-alcoholic cirrhosis. Egypt used to be the country with the heaviest hepatitis C virus (HCV) burden. The relationship between HCV and HCC is an important research area. In Egypt, HCC is a significant public health problem. A possible cause for the increasing rates of detection of HCC in Egypt is the mass screening program that was carried by the government for detecting and treating HCV. A multidisciplinary approach is now widely applied to HCC management in health centers all over Egypt. Different treatment modalities are available in Egypt, with success rates comparable to global rates. The Egyptian health authorities have made the elimination of HCV from Egypt a special priority, and this approach should lead to a decrease in number of HCC cases in the near future. In this article we review the current situation of HCC in Egypt, including epidemiological aspects, relevant risk factors for HCC development, strategies, and efforts established by health authorities for the screening and prevention of both HCV and HCC in Egypt. We highlight the different modalities for HCC treatment.
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Affiliation(s)
- Reem Ezzat
- Internal Medicine Department, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Mohamed Eltabbakh
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt
| | - Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo 11795, Cairo, Egypt
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Chen M, Hu G, Zhou X, Peng Z, Wen W. Hsa_circ_0016788 regulates hepatocellular carcinoma progression via miR-506-3p/poly-adenosine diphosphate-ribose polymerase. J Gastroenterol Hepatol 2021; 36:3457-3468. [PMID: 34340259 DOI: 10.1111/jgh.15635] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 07/12/2021] [Accepted: 07/20/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide. Recent researches have shown that circular RNAs (circRNAs) could affect the progress of HCC, but the mechanism is still indistinct. In this work, we explored the roles of circRNA_0016788 in HCC. METHODS The levels of hsa_circ_0016788, microRNA-506-3p (miR-506-3p), and mRNA of poly-adenosine diphosphate-ribose polymerase, member 14 (PARP14) were detected by quantitative real-time reverse transcription-polymerase chain reaction in HCC tissues. Meanwhile, the level of PARP14 was quantified by Western blot analysis. Besides, the cell functions were examined by commercial kit, Cell Counting Kit-8 assay, EdU assay, colony formation assay, flow cytometry assay, Western blot, and transwell assay. Furthermore, the interplay between miR-506-3p and hsa_circ_0016788 or PARP14 was detected by dual-luciferase reporter assay. Eventually, the in vivo experiments were applied to measure the role of hsa_circ_0016788. RESULTS The levels of hsa_circ_0016788 and PARP14 were upregulated, and the miR-506-3p level was decreased in HCC tissues in contrast to that in normal tissues. For functional analysis, hsa_circ_0016788 deficiency inhibited cell glycolysis metabolism, cell vitality, cell proliferation, colony formation, and invasion in HCC cells whereas promoted cell apoptosis. Moreover, miR-506-3p was confirmed to repress the progression of HCC cells by suppressing PARP14. In mechanism, hsa_circ_0016788 acted as a miR-506-3p sponge to regulate the level of PARP14. In addition, hsa_circ_0016788 knockdown also inhibited tumor growth in vivo. CONCLUSION Hsa_circ_0016788 facilitates the development of HCC through increasing PARP14 expression by regulating miR-506-3p, which also offered an underlying targeted therapy for HCC treatment.
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Affiliation(s)
- Ming Chen
- The First Affiliated Hospital, Department of Gastroenterology and Hepatology, Hengyang Medical School, University of South China, Hengyang, China
| | - Guangsheng Hu
- The First Affiliated Hospital, Department of Gastroenterology and Hepatology, Hengyang Medical School, University of South China, Hengyang, China
| | - Xin Zhou
- Department of Gastroenterology, Zibo Central Hospital of Shandong Province, Zibo, China
| | - Zhong Peng
- The First Affiliated Hospital, Department of Gastroenterology and Hepatology, Hengyang Medical School, University of South China, Hengyang, China
| | - Wu Wen
- The First Affiliated Hospital, Department of Hepato-Biliary-Pancreatic Surgery, Hengyang Medical School, University of South China, Hengyang, China
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Dark and bright side of targeting fibroblast growth factor receptor 4 in the liver. J Hepatol 2021; 75:1440-1451. [PMID: 34364916 DOI: 10.1016/j.jhep.2021.07.029] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 07/09/2021] [Accepted: 07/26/2021] [Indexed: 12/12/2022]
Abstract
Fibroblast growth factor (FGF) receptor 4 (FGFR4) and its cognate ligand, FGF19, are implicated in a range of cellular processes, including differentiation, metabolism and proliferation. Indeed, their aberrant activation has been associated with the development of hepatic tumours. Despite great advances in early diagnosis and the development of new therapies, liver cancer is still associated with a high mortality rate, owing primarily to high molecular heterogeneity and unclear molecular targeting. The development of FGFR4 inhibitors is a promising tool in patients with concomitant supraphysiological levels of FGF19 and several clinical trials are testing these treatments for patients with advanced hepatocellular carcinoma (HCC). Conversely, using FGF19 analogues to activate FGFR4-KLOTHO β represents a novel therapeutic strategy in patients presenting with cholestatic liver disorders and non-alcoholic steatohepatitis, which could potentially prevent the development of metabolic HCC. Herein, we provide an overview of the currently available therapeutic options for targeting FGFR4 in HCC and other liver diseases, highlighting the need to carefully stratify patients and personalise therapeutic strategies.
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36
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Rahadiani N, Andhini Retnowulan I, Stephanie M, Rini Handjari D, Krisnuhoni E. β-Catenin Expression and Its Association with Prognostic Factors in Hepatocellular Carcinoma: A Study on Alpha-fetoprotein, Histologic Grade, and Microvascular Invasion. Open Access Maced J Med Sci 2021. [DOI: 10.3889/oamjms.2021.6123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Background. Hepatocellular carcinoma (HCC), the most common primary liver cancer. In addition to its high incidence, the disease burden is high due to its poor prognosis and high recurrence rate. Some of the currently known clinicopathologic prognostic factors include alpha-fetoprotein (AFP) level, histologic grade, and microvascular invasion. At the molecular level, β-catenin is one of the most common driver mutation found in HCC. The Wnt/β-catenin pathway regulates cellular processes related to initiation, growth, survival, migration, differentiation, and apoptosis. Although the underlying pathogenesis of hepatocarcinogenesis is known, clinical application warrants a greater understanding of the molecular characteristics and tumor phenotype, especially for determining the prognosis. This study aims to analyze the expression of β-catenin and its association with AFP, histologic grade, and microvascular invasion. Materials and methods. Thirty-five samples of surgically resected HCCs at Cipto Mangunkusumo National Referral Hospital were examined. Diagnoses were made based on histopathological and immunohistochemical findings followed by β-catenin staining. β-catenin expression was analyzed to determine difference between variables. Results and conclusions. Here we show that β-catenin expression is significantly associated with low serum alpha-fetoprotein and well to moderate differentiation Implications. Strong nuclear β-catenin expression implies better prognosis in HCC.
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37
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Mahn R, Sadeghlar F, Bartels A, Zhou T, Weismüller T, Kupczyk P, Meyer C, Gaertner FC, Toma M, Vilz T, Knipper P, Glowka T, Manekeller S, Kalff J, Strassburg CP, Gonzalez-Carmona MA. Multimodal and systemic therapy with cabozantinib for treatment of recurrent hepatocellular carcinoma after liver transplantation: A case report with long term follow-up outcomes. Medicine (Baltimore) 2021; 100:e27082. [PMID: 34559100 PMCID: PMC8462617 DOI: 10.1097/md.0000000000027082] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 08/12/2021] [Indexed: 01/05/2023] Open
Abstract
RATIONALE Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains a major therapeutic challenge. In recent years, new molecular-targeted therapies, such as cabozantinib, have been approved for the treatment of advanced HCC. However, clinical experience with these new drugs in the treatment of HCC in the LT setting is very limited. PATIENT CONCERNS In 2003, a 36-year-old woman was referred to the hospital with right upper abdominal pain. DIAGNOSIS An initial ultrasound of the liver demonstrated a large unclear lesion of the left lobe of the liver. The magnet resonance imaging findings confirmed a multifocal inoperable HCC in a non-cirrhotic liver. Seven years after receiving a living donor LT, pulmonary and intra-hepatic recurrence of the HCC was radiologically diagnosed and histologically confirmed. INTERVENTIONS Following an interdisciplinary therapy concept consisting of surgical, interventional-radiological (with radiofrequency ablation [RFA]) as well as systemic treatment, the patient achieved a survival of more than 10 years after tumor recurrence. As systemic first line therapy with sorafenib was accompanied by grade 3 to 4 toxicities, such as mucositis, hand-foot skin reaction, diarrhea, liver dysfunction, and hyperthyroidism, it had to be discontinued. After switching to cabozantinib from June 2018 to April 2020, partial remission of all tumor manifestations was achieved. The treatment of the remaining liver metastasis could be completed by RFA. The therapy with cabozantinib was well tolerated, only mild arterial hypertension and grade 1 to 2 mucositis were observed. Liver transplant function was stable during the therapy, no drug interaction with immunosuppressive drugs was observed. OUTCOMES More than 10 years survival after recurrence of HCC after living-donor LT due to intensive multimodal therapy concepts, including surgery, RFA, and systemic therapy with cabozantinib in the second line therapy. LESSONS In conclusion, this report highlights the tolerability and effectiveness of cabozantinib for the treatment of HCC recurrence after LT. We show that our patient with a late recurrence of HCC after LT benefitted from intensive multimodal therapy concepts, including surgery, RFA, and systemic therapy.
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Affiliation(s)
- Robert Mahn
- Department of Internal Medicine I, University Hospital Bonn, Germany
| | | | - Alexandra Bartels
- Department of Internal Medicine I, University Hospital Bonn, Germany
| | - Taotao Zhou
- Department of Internal Medicine I, University Hospital Bonn, Germany
| | - Tobias Weismüller
- Department of Internal Medicine I, University Hospital Bonn, Germany
| | | | - Carsten Meyer
- Department of Radiology, University Hospital Bonn, Germany
| | | | - Marieta Toma
- Department of Pathology, University Hospital Bonn, Germany
| | - Tim Vilz
- Department of Visceral Surgery, University Hospital Bonn, Germany
| | - Petra Knipper
- Department of Visceral Surgery, University Hospital Bonn, Germany
| | - Tim Glowka
- Department of Visceral Surgery, University Hospital Bonn, Germany
| | | | - Jörg Kalff
- Department of Visceral Surgery, University Hospital Bonn, Germany
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Greten TF, Abou-Alfa GK, Cheng AL, Duffy AG, El-Khoueiry AB, Finn RS, Galle PR, Goyal L, He AR, Kaseb AO, Kelley RK, Lencioni R, Lujambio A, Mabry Hrones D, Pinato DJ, Sangro B, Troisi RI, Wilson Woods A, Yau T, Zhu AX, Melero I. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of hepatocellular carcinoma. J Immunother Cancer 2021; 9:e002794. [PMID: 34518290 PMCID: PMC8438858 DOI: 10.1136/jitc-2021-002794] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/02/2021] [Indexed: 12/11/2022] Open
Abstract
Patients with advanced hepatocellular carcinoma (HCC) have historically had few options and faced extremely poor prognoses if their disease progressed after standard-of-care tyrosine kinase inhibitors (TKIs). Recently, the standard of care for HCC has been transformed as a combination of the immune checkpoint inhibitor (ICI) atezolizumab plus the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab was shown to offer improved overall survival in the first-line setting. Immunotherapy has demonstrated safety and efficacy in later lines of therapy as well, and ongoing trials are investigating novel combinations of ICIs and TKIs, in addition to interventions earlier in the course of disease or in combination with liver-directed therapies. Because HCC usually develops against a background of cirrhosis, immunotherapy for liver tumors is complex and oncologists need to account for both immunological and hepatological considerations when developing a treatment plan for their patients. To provide guidance to the oncology community on important concerns for the immunotherapeutic care of HCC, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel of experts to develop a clinical practice guideline (CPG). The expert panel drew on the published literature as well as their clinical experience to develop recommendations for healthcare professionals on these important aspects of immunotherapeutic treatment for HCC, including diagnosis and staging, treatment planning, immune-related adverse events (irAEs), and patient quality of life (QOL) considerations. The evidence- and consensus-based recommendations in this CPG are intended to give guidance to cancer care providers treating patients with HCC.
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Affiliation(s)
- Tim F Greten
- Thoracic and GI Malignancies Branch, National Cancer Institute, Bethesda, Maryland, USA
| | - Ghassan K Abou-Alfa
- Memorial Sloan Kettering Cancer Center, New York, New York, USA
- Weill Medical College at Cornell University, New York, New York, USA
| | - Ann-Lii Cheng
- Department of Medical Oncology, National Taiwan University Cancer Center and National Taiwan University Hospital, Taipei, Taiwan
| | - Austin G Duffy
- The Mater Hospital/University College Dublin, Dublin, Ireland
| | - Anthony B El-Khoueiry
- Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA
| | - Richard S Finn
- David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA
| | | | - Lipika Goyal
- Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Aiwu Ruth He
- Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia, USA
| | - Ahmed O Kaseb
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Robin Kate Kelley
- Department of Medicine (Hematology/Oncology), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California, USA
| | - Riccardo Lencioni
- Department of Radiology, University of Pisa School of Medicine, Pisa, Italy
- Miami Cancer Institute, Miami, Florida, USA
| | - Amaia Lujambio
- Oncological Sciences Department, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Donna Mabry Hrones
- Thoracic and GI Malignancies Branch, National Cancer Institute, Bethesda, Maryland, USA
| | - David J Pinato
- Department of Surgery & Cancer, Imperial College London, London, UK
| | - Bruno Sangro
- Clinica Universidad de Navarra-Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | | | - Andrea Wilson Woods
- Blue Faery: The Adrienne Wilson Liver Cancer Association, Birmingham, Alabama, USA
| | - Thomas Yau
- Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong
| | - Andrew X Zhu
- Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
- Jiahui Health, Jiahui International Cancer Center, Shanghai, China
| | - Ignacio Melero
- Clinica Universidad de Navarra-Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain
- Foundation for Applied Medical Research (FIMA), Pamplona, Spain
- Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain
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Nischalke HD, Fischer J, Klüners A, Matz-Soja M, Krämer B, Langhans B, Goeser F, Soyka M, Stickel F, Spengler U, Nattermann J, Strassburg CP, Berg T, Lutz P. A genetic variant in toll-like receptor 5 is linked to chemokine levels and hepatocellular carcinoma in steatohepatitis. Liver Int 2021; 41:2139-2148. [PMID: 34051061 DOI: 10.1111/liv.14980] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 04/26/2021] [Accepted: 05/19/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS Bacterial translocation drives liver disease progression. We investigated whether functional genetic variants in toll-like receptor 5 (TLR5), the receptor for bacterial flagellin, affect the risk for hepatocellular carcinoma (HCC). METHODS Healthy controls (n = 212), patients with alcohol abuse without liver disease (n = 382), and patients from a discovery cohort of alcohol-associated cirrhosis (n = 372 including 79 HCC cases), a validation cohort of alcohol-associated cirrhosis (n = 355 including 132 HCC cases), and a cohort of cirrhosis due to nonalcoholic steatohepatitis (NASH) (n = 145 including 62 HCC cases) were genotyped for the TLR5 rs5744174 and rs5744168 polymorphisms. Chemokine levels were measured by ELISA in patients' sera and supernatants of flagellin-stimulated healthy monocytes. RESULTS Frequency of the TLR5 rs5744174 TT genotype was similar in healthy controls (33%), controls with alcohol abuse (34%), and patients with alcohol-associated cirrhosis in the discovery (28%), validation (33%), and NASH cohort (31%). The TT genotype was enriched in patients with versus without HCC in the discovery, validation, and NASH cohort (41% vs 25%; 39% vs 29%; 40% vs 24%; p < .05 each). This genotype remained a risk factor for HCC (OR = 1.9; p = .01) after multivariate correction for age, gender, diabetes, and carriage of the PNPLA3 148M variant. Interleukin-8 induction in monocytes from healthy controls and serum levels of interleukin-8 and CXCL1 from cirrhotic patients with the TT genotype were significantly increased versus C allele carriers. CONCLUSION The TLR5 rs5744174 polymorphism, affecting immune response to flagellin, is linked to occurrence of HCC in cirrhosis caused by steatohepatitis.
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Affiliation(s)
- Hans Dieter Nischalke
- Department of Internal Medicine I, University Hospital, University of Bonn, Bonn, Germany
| | - Janett Fischer
- Division of Hepatology, Department of Oncology, Gastroenterology, Hepatology, Pulmonology and Infectious Diseases, Leipzig University Medical Center, Leipzig, Germany
| | - Alexandra Klüners
- Department of Internal Medicine I, University Hospital, University of Bonn, Bonn, Germany
| | - Madlen Matz-Soja
- Division of Hepatology, Department of Oncology, Gastroenterology, Hepatology, Pulmonology and Infectious Diseases, Leipzig University Medical Center, Leipzig, Germany
| | - Benjamin Krämer
- Department of Internal Medicine I, University Hospital, University of Bonn, Bonn, Germany
| | - Bettina Langhans
- Department of Internal Medicine I, University Hospital, University of Bonn, Bonn, Germany
| | - Felix Goeser
- Department of Internal Medicine I, University Hospital, University of Bonn, Bonn, Germany
| | - Michael Soyka
- Psychiatric Hospital, Ludwig Maximilians University, Munich, Germany
| | - Felix Stickel
- Department of Gastroenterology and Hepatology, University Hospital of Zürich, Zürich, Switzerland
| | - Ulrich Spengler
- Department of Internal Medicine I, University Hospital, University of Bonn, Bonn, Germany
| | - Jacob Nattermann
- Department of Internal Medicine I, University Hospital, University of Bonn, Bonn, Germany
| | - Christian P Strassburg
- Department of Internal Medicine I, University Hospital, University of Bonn, Bonn, Germany
| | - Thomas Berg
- Division of Hepatology, Department of Oncology, Gastroenterology, Hepatology, Pulmonology and Infectious Diseases, Leipzig University Medical Center, Leipzig, Germany
| | - Philipp Lutz
- Department of Internal Medicine I, University Hospital, University of Bonn, Bonn, Germany
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Oh JH, Goh MJ, Park Y, Kim J, Kang W, Sinn DH, Gwak GY, Choi MS, Lee JH, Koh KC, Paik SW, Paik YH. Different Performance of Liver Stiffness Measurement According to Etiology and Outcome for the Prediction of Liver-Related Events. Dig Dis Sci 2021; 66:2816-2825. [PMID: 32897445 DOI: 10.1007/s10620-020-06591-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 08/26/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND/AIMS Liver stiffness measurement (LSM) by transient elastography (TE) has shown promising results for prediction of hepatocellular carcinoma (HCC) and hepatic decompensation in patients with chronic liver disease (CLD). However, whether prognostic performance of TE differs according to etiology or type of outcome remains further clarification. METHODS Performance of LSM for the prediction of HCC and hepatic decompensation was analyzed in a cohort of 4026 patients with asymptomatic CLD. RESULTS During median 4.5 years of follow-up (range 3.0-6.2 years), liver-related events (LRE) were observed in 196 patients (166 with HCC, 45 with hepatic decompensation, and 15 with both). In the multivariate analysis, LSM was independent factor associated with LRE and showed high AUROC (0.78). When stratified by type of outcome and etiology of liver disease, LSM showed high AUROC for the prediction of HCC for patients with non-viral hepatitis (0.89), while it showed relatively low AUROC for the prediction of HCC for patients with viral hepatitis (0.75). For the prediction of hepatic decompensation, LSM showed high AUROC for patients with both viral- and non-viral hepatitis (0.90, 0.90, respectively). CONCLUSIONS LSM showed powerful prognostic role for the prediction of LRE in patients with CLD. Notably, HCC risk was not negligible in patients with viral hepatitis who showed LSM value < 10 kPa, indicating watchful attention for HCC is still needed for viral hepatitis patients with low LSM.
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Affiliation(s)
- Joo Hyun Oh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea
| | - Myung Ji Goh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea
| | - Yewan Park
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea
| | - Jihye Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea
| | - Wonseok Kang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea.
| | - Geum-Youn Gwak
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea
| | - Moon Seok Choi
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea
| | - Joon Hyeok Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea
| | - Kwang Cheol Koh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea
| | - Seung Woon Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea
| | - Yong-Han Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea
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Metallomic profile in non-cirrhotic hepatocellular carcinoma supports a phenomenon of metal metabolism adaptation in tumor cells. Sci Rep 2021; 11:14195. [PMID: 34244548 PMCID: PMC8271004 DOI: 10.1038/s41598-021-93369-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Accepted: 06/18/2021] [Indexed: 01/31/2023] Open
Abstract
We have previously described a form of hepatocellular carcinoma (HCC) in non-cirrhotic liver (HCC-NC) developed by Peruvian patients. We analyzed the metallomic profile in hepatic tissues from two independent cohorts exhibiting HCC-NC. Clinical, histopathological data, and HCC and non-tumoral liver (NTL) samples of 38 Peruvian and 38 French HCC-NC patients, were studied. Twelve metals were quantified using ICP/MS: Mn, Fe, Cu, Co, Zn, As, Se, Rb, Mo, Cd, Pb, and Sn. Associations between metals and survival were assessed. Our data showed significant differences between cohorts. Mean ages were 40.6 ± 20, 67.5 ± 9 years old for Peruvians and French, respectively. Fifty percent of the Peruvian patients were positive for the HBsAg, versus 3% in French patients. Mn, Cu, Zn, As, Se, Rb, Mo, Cd, Sn metal concentrations were higher in NTL of Peruvians. Importantly, metal concentrations were lower in HCC areas compared to NTL tissues in both cohorts, except for Cu for which mean concentration was higher in HCC (p < 0.05). Se concentration in HCC was associated with extended survival only in Peruvians. Our data, obtained in Peruvian and French HCC-NC cohorts, highlights similarity in the metallomic profile of HCC compared to NTL during the hepatic tumorigenesis in these specific groups of patients.
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Li W, Li R, Zhao X, Lin X, Yu Y, Zhang J, Chen K, Chai W, Yan F. Differentiation of Hepatocellular Carcinoma from Hepatic Hemangioma and Focal Nodular Hyperplasia using Computed Tomographic Spectral Imaging. J Clin Transl Hepatol 2021; 9:315-323. [PMID: 34221917 PMCID: PMC8237149 DOI: 10.14218/jcth.2020.00173] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 02/26/2021] [Accepted: 03/07/2021] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND AND AIMS Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy. This study was designed to investigate the value of computed tomography (CT) spectral imaging in differentiating HCC from hepatic hemangioma (HH) and focal nodular hyperplasia (FNH). METHODS This was a retrospective study of 51 patients who underwent spectral multiple-phase CT at 40-140 keV during the arterial phase (AP) and portal venous phase (PP). Slopes of the spectral curves, iodine density, water density derived from iodine- and water-based material decomposition images, iodine uptake ratio (IUR), normalized iodine concentration, and the ratio of iodine concentration in liver lesions between AP and PP were measured or calculated. RESULTS As energy level decreased, the CT values of HCC (n=31), HH (n=17), and FNH (n=7) increased in both AP and PP. There were significant differences in IUR in the AP, IUR in the PP, normalized iodine concentration in the AP, slope in the AP, and slope in the PP among HCC, HH, and FNH. The CT values in AP, IUR in the AP and PP, normalized iodine concentration in the AP, slope in the AP and PP had high sensitivity and specificity in differentiating HH and HCC from FNH. Quantitative CT spectral data had higher sensitivity and specificity than conventional qualitative CT image analysis during the combined phases. CONCLUSIONS Mean CT values at low energy (40-90 keV) and quantitative analysis of CT spectral data (IUR in the AP) could be helpful in the differentiation of HCC, HH, and FNH.
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Affiliation(s)
- Weixia Li
- Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ruokun Li
- Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiangtian Zhao
- Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China
| | - Xiaozhu Lin
- Department of Nuclear Medicine, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yixing Yu
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Jing Zhang
- Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Kemin Chen
- Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weimin Chai
- Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Fuhua Yan
- Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Correspondence to: Fuhua Yan, Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 197 Ruijin Erlu, Huangpu District, Shanghai 200025, China. ORCID: https://orcid.org/0000-0002-6385-499X. Tel: +86-21-6437-0045-665724, Fax: +86-21-6384-2916, E-mail:
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43
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RETROSPECTIVE EVALUATION OF HEPATOCELLULAR NEOPLASMS IN NILE LECHWE ( KOBUS MEGACEROS) FROM TWO FLORIDA ZOOLOGICAL INSTITUTIONS. J Zoo Wildl Med 2021; 51:678-686. [PMID: 33480545 DOI: 10.1638/2020-0038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/11/2020] [Indexed: 11/21/2022] Open
Abstract
This case series describes hepatocellular neoplasms in 10 Nile lechwe (Kobus megaceros) at two separate zoological institutions in Florida. Histologically, the neoplasms were classified as hepatocellular carcinoma (n = 7), hepatocellular adenoma (n = 2), and hepatobiliary carcinoma (n = 1). Common clinical signs were nonspecific and included thin body condition (n =7), lethargy (n =6), lameness (n =3), and acute recumbency (n =5). Four males and six females were affected, and the mean age at death was 12.7 yr with a range of 4-18 yr. All cases were diagnosed postmortem, and metastasis to various sites, including lung, lymph nodes, and omentum, was found in 40% of cases (n = 4). A single case of hepatocellular carcinoma in a Nile lechwe was described in 2007; however, this is the first reported series of neoplasms in Reduncinae. The pathogenesis behind the development of hepatocellular neoplasms in Nile lechwe has not yet been identified.
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Shavelle RM, Kwak JH, Saur R, Brooks JC, Rosenthal P. Life Expectancy after Liver Transplantation for Non-Cirrhotic Hepatocellular Carcinoma. Prog Transplant 2021; 31:117-125. [PMID: 33722096 DOI: 10.1177/15269248211002793] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Hepatocelluar carcinoma typically occurs with underlying cirrhosis. However roughly 20% of cases arise in a non-cirrhotic liver. There is limited literature that addresses the long-term survival of the narrow subgroup who received transplantation. For such patients we sought to calculate life expectancies both at time of transplant and several years later, stratified by key risk factors, and to determine if survival has improved in recent years. Such information can be helpful in making treatment decisions. METHODS Data on 4,373 non-cirrhotic HCC patients who underwent liver transplantation in the MELD era (2002-2018) from the United States OPTN database were analyzed using the Cox proportional hazards regression model and life table methods. RESULTS Demographic and past medical history factors related to survival were patient age, donor age over 20, and the presence of ascites or severe hepatic encephalopathy. Survival did not vary by race or sex. HCC-specific factors significantly related to survival were the total number of tumors, extrahepatic spread, lymph node involvement, satellite lesions, micro- or macrovascular invasion, tumor differentiation (grade), and pre-transplant treatment. Survival improved over the study period, at 4% per calendar year during the first 5 years post transplant and 1% per year thereafter. CONCLUSIONS Life expectancy in non-cirrhotic HCC transplant patients is much reduced from normal, and varies according to age and tumor-related factors. Survival improved modestly over the study period.
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Affiliation(s)
| | - Ji Hun Kwak
- Life Expectancy Project, San Francisco, CA, USA
| | - Rachel Saur
- Life Expectancy Project, San Francisco, CA, USA
| | | | - Philip Rosenthal
- Pediatric Hepatology, 8785University of California, San Francisco, CA, USA
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[State of the art in the diagnostics of hepatocellular carcinoma and current treatment options]. Radiologe 2021; 61:213-226. [PMID: 33464405 DOI: 10.1007/s00117-020-00798-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Hepatocellular carcinoma (HCC) is the most frequent primary hepatic malignancy and arises most often based on liver cirrhosis. Of the HCC 80-85% demonstrate a typical contrast medium behavior in imaging, characterized by arterial hypervascularization followed by wash-out in the portal or late venous phase. This specific contrast behavior is diagnostic for HCC in patients at risk. The use of liver-specific contrast agents increases the sensitivity for diagnosis of HCC and can facilitate the differentiation from other liver lesions. At initial diagnosis approximately 50% of HCC are solitary, 40% multifocal and 10% diffuse. Depending on the tumor extent and stage, therapeutic options in patients with HCC include local treatment (resection, ablation, radiation, liver transplantation), locoregional measures (transarterial chemoembolization, selective internal radiotherapy) or systemic therapy (including immunotherapy), either as a stand-alone procedure or in various combinations.
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46
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Shin J, Yu JH, Jin YJ, Lee JW. Incidence and Clinical Features of Hepatitis C Virus-associated Hepatocellular Carcinoma Patients without Liver Cirrhosis in Hepatitis B Virus-endemic Area. JOURNAL OF LIVER CANCER 2021; 21:34-44. [PMID: 37384274 PMCID: PMC10035726 DOI: 10.17998/jlc.21.1.34] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 12/22/2020] [Accepted: 01/11/2021] [Indexed: 06/30/2023]
Abstract
Background/objective Hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) is rarely observed in patients without liver cirrhosis (LC). We evaluated the incidence and clinical feature of HCV-associated HCC patients with or without LC. Methods The medical records of 1,516 patients diagnosed as having primary HCC at our hospital between January 2005 and December 2017 were retrospectively reviewed. Of these, 154 (10.2%) HCV-associated HCC patients were analyzed. LC was diagnosed histologically or clinically. Results Seventeen (11.0%) of the 154 patients had non-cirrhotic HCC, and all were of Child-Turcotte-Pugh (CTP) class A, Among the 17 patients, 88.2% were male, all had nodular type HCC, and only 2 (11.8%) were under HCC surveillance. Median overall survival (OS) of HCV-associated HCC patients with and without LC was 15 months and 37 months, respectively. Cumulative OS rates were not different between non-cirrhotic patients and cirrhotic patients with CTP class A (P=0.229). Cumulative OS rates were significantly higher in non-cirrhotic patients than in cirrhotic patients of CTP class B (P<0.001) or C (P<0.001). Multivariate analyses showed serum AST (hazard ratio [HR] 1.01, P=0.003) and AFP levels (HR 1.01, P=0.016), antiviral therapy (HR 0.25, P=0.022), and LC of CTP class B (HR, 5.24, P=0.006) or C (HR 21.79, P<0.001) were significantly associated with prognosis in HCV-associated HCC patients. Conclusions HCC in a non-cirrhotic liver was found in 11% of HCV-associated HCC patients. OSs of HCV-associated HCC patients were better in those of CTP A, regardless of LC than in those with LC of CTP class B or C.
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Affiliation(s)
- Jongbeom Shin
- Division of Gastroenterology, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Jung Hwan Yu
- Division of Gastroenterology, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Young-Joo Jin
- Division of Gastroenterology, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Jin-Woo Lee
- Division of Gastroenterology, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
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Stepien M, Keski-Rahkonen P, Kiss A, Robinot N, Duarte-Salles T, Murphy N, Perlemuter G, Viallon V, Tjønneland A, Rostgaard-Hansen AL, Dahm CC, Overvad K, Boutron-Ruault MC, Mancini FR, Mahamat-Saleh Y, Aleksandrova K, Kaaks R, Kühn T, Trichopoulou A, Karakatsani A, Panico S, Tumino R, Palli D, Tagliabue G, Naccarati A, Vermeulen RCH, Bueno-de-Mesquita HB, Weiderpass E, Skeie G, Ramón Quirós J, Ardanaz E, Mokoroa O, Sala N, Sánchez MJ, Huerta JM, Winkvist A, Harlid S, Ohlsson B, Sjöberg K, Schmidt JA, Wareham N, Khaw KT, Ferrari P, Rothwell JA, Gunter M, Riboli E, Scalbert A, Jenab M. Metabolic perturbations prior to hepatocellular carcinoma diagnosis: Findings from a prospective observational cohort study. Int J Cancer 2021; 148:609-625. [PMID: 32734650 DOI: 10.1002/ijc.33236] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 06/16/2020] [Accepted: 06/26/2020] [Indexed: 12/19/2022]
Abstract
Hepatocellular carcinoma (HCC) development entails changes in liver metabolism. Current knowledge on metabolic perturbations in HCC is derived mostly from case-control designs, with sparse information from prospective cohorts. Our objective was to apply comprehensive metabolite profiling to detect metabolites whose serum concentrations are associated with HCC development, using biological samples from within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (>520 000 participants), where we identified 129 HCC cases matched 1:1 to controls. We conducted high-resolution untargeted liquid chromatography-mass spectrometry-based metabolomics on serum samples collected at recruitment prior to cancer diagnosis. Multivariable conditional logistic regression was applied controlling for dietary habits, alcohol consumption, smoking, body size, hepatitis infection and liver dysfunction. Corrections for multiple comparisons were applied. Of 9206 molecular features detected, 220 discriminated HCC cases from controls. Detailed feature annotation revealed 92 metabolites associated with HCC risk, of which 14 were unambiguously identified using pure reference standards. Positive HCC-risk associations were observed for N1-acetylspermidine, isatin, p-hydroxyphenyllactic acid, tyrosine, sphingosine, l,l-cyclo(leucylprolyl), glycochenodeoxycholic acid, glycocholic acid and 7-methylguanine. Inverse risk associations were observed for retinol, dehydroepiandrosterone sulfate, glycerophosphocholine, γ-carboxyethyl hydroxychroman and creatine. Discernible differences for these metabolites were observed between cases and controls up to 10 years prior to diagnosis. Our observations highlight the diversity of metabolic perturbations involved in HCC development and replicate previous observations (metabolism of bile acids, amino acids and phospholipids) made in Asian and Scandinavian populations. These findings emphasize the role of metabolic pathways associated with steroid metabolism and immunity and specific dietary and environmental exposures in HCC development.
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Affiliation(s)
- Magdalena Stepien
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Pekka Keski-Rahkonen
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Agneta Kiss
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Nivonirina Robinot
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Talita Duarte-Salles
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
- Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Barcelona, Spain
| | - Neil Murphy
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Gabriel Perlemuter
- INSERM UMRS U996 - Intestinal Microbiota, Macrophages and Liver Inflammation, Clamart, France
- Université Paris-Sud, Clamart, France
- AP-HP, Hepato-gastroenterology and Nutrition, Antoine-Béclère Hospital, Clamart, France
| | - Vivian Viallon
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Anne Tjønneland
- Diet, Genes and Environment Unit, Danish Cancer Society Research Center, Copenhagen, Denmark
| | | | - Christina C Dahm
- Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark
| | - Kim Overvad
- Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark
- Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark
| | - Marie-Christine Boutron-Ruault
- CESP, Faculté de médecine-Université Paris-Sud, Faculté de médecine-UVSQ, INSERM, Université Paris-Saclay, Villejuif, France
- Institut Gustave Roussy, Villejuif, France
| | - Francesca Romana Mancini
- CESP, Faculté de médecine-Université Paris-Sud, Faculté de médecine-UVSQ, INSERM, Université Paris-Saclay, Villejuif, France
- Institut Gustave Roussy, Villejuif, France
| | - Yahya Mahamat-Saleh
- CESP, Faculté de médecine-Université Paris-Sud, Faculté de médecine-UVSQ, INSERM, Université Paris-Saclay, Villejuif, France
- Institut Gustave Roussy, Villejuif, France
| | - Krasimira Aleksandrova
- Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany
| | - Rudolf Kaaks
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Tilman Kühn
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Antonia Trichopoulou
- Hellenic Health Foundation, Athens, Greece
- WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept. of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Anna Karakatsani
- Hellenic Health Foundation, Athens, Greece
- Second Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, Haidari, Greece
| | - Salvatore Panico
- Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy
| | - Rosario Tumino
- Cancer Registry and Histopathology Department, Provincial Health Authority (ASP) Ragusa, Ragusa, Italy
| | - Domenico Palli
- Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy
| | - Giovanna Tagliabue
- Lombardy Cancer Registry Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Alessio Naccarati
- Molecular and Genetic Epidemiology Unit, Italian Institute for Genomic Medicine (IIGM) Torino, Torino, Italy
| | - Roel C H Vermeulen
- Institute of Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands
| | - Hendrik Bastiaan Bueno-de-Mesquita
- Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
- Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
- Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Elisabete Weiderpass
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Guri Skeie
- Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
| | | | - Eva Ardanaz
- Navarra Public Health Institute, Pamplona, Spain
- IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
- CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain
| | - Olatz Mokoroa
- CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Public Health Division of Gipuzkoa, Biodonostia Research Institute, San Sebastian, Spain
| | - Núria Sala
- Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program and Translational Research Laboratory, Catalan Institute of Oncology (IDIBELL), Barcelona, Spain
| | - Maria-Jose Sánchez
- CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs. Granada. Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain
| | - José María Huerta
- CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain
| | - Anna Winkvist
- The Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
- Department of Public Health and Clinical Medicine, Nutrition Research, Umeå University, Umeå, Sweden
| | - Sophia Harlid
- Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
| | - Bodil Ohlsson
- Skåne University Hospital, Department of Internal Medicine, Lund University, Malmö, Sweden
| | - Klas Sjöberg
- Skåne University Hospital, Department of Gastroenterology and Nutrition, Lund University, Malmö, Sweden
| | - Julie A Schmidt
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Nick Wareham
- MRC Epidemiology Unit, University of Cambridge, Cambridge, UK
| | - Kay-Tee Khaw
- University of Cambridge, School of Clinical Medicine, Clinical Gerontology Unit, Addenbrooke's Hospital, Cambridge, UK
| | - Pietro Ferrari
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Joseph A Rothwell
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
- Institut Gustave Roussy, Villejuif, France
| | - Marc Gunter
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Elio Riboli
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Augustin Scalbert
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Mazda Jenab
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
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Mehta N, Bhavsar R, Das SP. Transplantation in hepatocellular carcinoma - controversies and recommendations: A review of current literature. INTERNATIONAL JOURNAL OF ADVANCED MEDICAL AND HEALTH RESEARCH 2021. [DOI: 10.4103/ijamr.ijamr_220_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Kontis EA. Biology of Liver Tumors and Outcomes of Liver Surgery. ANESTHESIA FOR HEPATICO-PANCREATIC-BILIARY SURGERY AND TRANSPLANTATION 2021:303-313. [DOI: 10.1007/978-3-030-51331-3_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Martínez-Mier G, Esquivel-Torres S, Casanova-Sánchez I, Escobar-Ríos A, Troche-Gutiérrez J, Yoldi-Aguirre C. Carcinoma hepatocelular en hígado no cirrótico: características clínicas y resultados en Veracruz, México. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2021; 86:4-12. [PMID: 32345506 DOI: 10.1016/j.rgmx.2019.11.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Revised: 10/29/2019] [Accepted: 11/28/2019] [Indexed: 02/06/2023]
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