Carla Pires Amaro, Michael J. Allen, Jennifer J. Knox, Erica S. Tsang, Howard J. Lim, Richard M. Lee-Ying, Kelvin W. Chan, Jessica Qian, Brandon M. Meyers, Alia Thawer, Sulaiman M. S. Al-Saadi, Tina Hsu, Ravi Ramjeesingh, Hatim Karachiwala, Tasnima Abedin, Vincent C. Tam
Background and Aims
A phase 3 trial showed lenvatinib to be effective and safe in the treatment of unresectable hepatocellular carcinoma (HCC), however, its performance in the real world and effect of dosing on survival are unclear.
Methods
From July 2018 to June 2020, HCC patients treated with lenvatinib from 10 Canadian cancer centres were included. Overall survival (OS) and progression-free survival (PFS) were retrospectively analysed and compared across first- and later lines use of lenvatinib. In patients receiving lenvatinib first-line, OS between different mean dose intensities and starting doses were compared.
Results
A total of 220 patients were included, of which 79% received lenvatinib as first-line therapy. For first-line versus later line treatment, median OS was 12.5 versus 11.8 months (P = .83) and median PFS was 7.6 versus 4.6 months (P = .27) respectively. Of patients receiving lenvatinib first-line, 54% started at full dose according to their weight. Median OS for patients starting lenvatinib at full- and reduced-dose was 12.3 and 15.8 months (P = .75) respectively. Median OS for patients with a mean dose intensity >66.7% compared ≤66.7% was 13.7 and 7.7 months (P = .01). In the multivariate analysis, dose intensity (>66.7 vs ≤66.7%) did not predict for OS [HR 0.70, 95% CI 0.42–1.18; P = .18]. The most common side effects were fatigue (59%), hypertension (41%) and decreased appetite (25%).
Conclusions
Lenvatinib appears to be effective in real-world practice regardless of the line of therapy. Dose modifications at the start or during treatment did not appear to significantly affect survival.
{"title":"Dosing, efficacy and safety of lenvatinb in the real-world treatment of hepatocellular carcinoma: Results from a Canadian database","authors":"Carla Pires Amaro, Michael J. Allen, Jennifer J. Knox, Erica S. Tsang, Howard J. Lim, Richard M. Lee-Ying, Kelvin W. Chan, Jessica Qian, Brandon M. Meyers, Alia Thawer, Sulaiman M. S. Al-Saadi, Tina Hsu, Ravi Ramjeesingh, Hatim Karachiwala, Tasnima Abedin, Vincent C. Tam","doi":"10.1002/lci2.59","DOIUrl":"10.1002/lci2.59","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>A phase 3 trial showed lenvatinib to be effective and safe in the treatment of unresectable hepatocellular carcinoma (HCC), however, its performance in the real world and effect of dosing on survival are unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>From July 2018 to June 2020, HCC patients treated with lenvatinib from 10 Canadian cancer centres were included. Overall survival (OS) and progression-free survival (PFS) were retrospectively analysed and compared across first- and later lines use of lenvatinib. In patients receiving lenvatinib first-line, OS between different mean dose intensities and starting doses were compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 220 patients were included, of which 79% received lenvatinib as first-line therapy. For first-line versus later line treatment, median OS was 12.5 versus 11.8 months (<i>P</i> = .83) and median PFS was 7.6 versus 4.6 months (<i>P</i> = .27) respectively. Of patients receiving lenvatinib first-line, 54% started at full dose according to their weight. Median OS for patients starting lenvatinib at full- and reduced-dose was 12.3 and 15.8 months (<i>P</i> = .75) respectively. Median OS for patients with a mean dose intensity >66.7% compared ≤66.7% was 13.7 and 7.7 months (<i>P</i> = .01). In the multivariate analysis, dose intensity (>66.7 vs ≤66.7%) did not predict for OS [HR 0.70, 95% CI 0.42–1.18; <i>P</i> = .18]. The most common side effects were fatigue (59%), hypertension (41%) and decreased appetite (25%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Lenvatinib appears to be effective in real-world practice regardless of the line of therapy. Dose modifications at the start or during treatment did not appear to significantly affect survival.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"3 3","pages":"119-127"},"PeriodicalIF":0.0,"publicationDate":"2022-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.59","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43812995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nishal Ravindran, Amol Agarwal, Feng Li, P. Thuluvath
The guidelines recommend surveillance with liver ultrasound (US) for early detection of hepatocellular carcinoma (HCC). The accuracy of US is operator‐dependent and is limited in those with severe obesity or ascites. Magnetic resonance imaging (MRI) may have higher accuracy for detecting HCC, especially early HCC.
{"title":"Liver ultrasound in cirrhosis is inadequate for hepatocellular carcinoma surveillance compared to magnetic resonance imaging","authors":"Nishal Ravindran, Amol Agarwal, Feng Li, P. Thuluvath","doi":"10.1002/lci2.57","DOIUrl":"https://doi.org/10.1002/lci2.57","url":null,"abstract":"The guidelines recommend surveillance with liver ultrasound (US) for early detection of hepatocellular carcinoma (HCC). The accuracy of US is operator‐dependent and is limited in those with severe obesity or ascites. Magnetic resonance imaging (MRI) may have higher accuracy for detecting HCC, especially early HCC.","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"3 1","pages":"113 - 118"},"PeriodicalIF":0.0,"publicationDate":"2022-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45976239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tuul Purevsambuu, Simona Bota, Florian Hucke, Harald Hofer, Peter Ferenci, Wolfgang Sieghart, Markus Peck-Radosavljevic
Introduction
Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death worldwide with increasing incidence. Effective antiviral treatment for chronic hepatitis C (CHC) became available in the last 7 years but despite the WHO Hepatitis elimination targets, they are not universally available today in all regions for all the patients, indicating still a bleak outlook for CHC-associated HCC in the next decades.
Aim
To assess the HCC incidence in relation to interferon (IFN)-based antiviral treatment response and baseline characteristics of a large cohort of chronic hepatitis C (CHC) patients from a single institution.
Methods
We retrospectively collected data of CHC patients, who were diagnosed between 1989 and 2011 and treated at the AKH-University Hospital of Vienna before the introduction of direct-acting antiviral (DAA) only therapy. We analysed the HCC incidence in patients with a sustained virological response (SVR) and without SVR according to the patients' baseline characteristics.
Results
Our study included 2134 patients, who were treated or not treated with IFN-based antiviral treatment and had long-term follow-up available. The overall HCC incidence in this cohort was 6.2% (132 HCC cases over a median follow-up period of 9 years). According to the baseline fibrosis stage, the overall HCC incidence was: 1.1% in patients with baseline fibrosis stage F0-2, 8.2% in F3 and 20.6% in F4 patients. The HCC incidence was significantly higher in non-SVR and no-treatment group as compared with SVR patients: 12.4% vs 1.9%, P < .0001, 7.3% vs 1.9%, P < .0001. In multivariate analysis, lower platelet count (odds ratio-OR = -0.1, 95% CI: 0.15-0.63), for the SVR group and presence of cirrhosis (OR = 3.6, 95% CI: 1.59-8.17), ALBI grade >=2 (OR = 2.3, 95% CI: 1.0-5.3) for the non-SVR group were independently associated with HCC occurrence. For the group of patients with no treatment, the only predictor for HCC was high baseline alpha-fetoprotein values (OR = 10.2, 95% CI: 2.2-47.9).
Conclusion
The achievement of SVR significantly reduces the risk for HCC occurrence during long-term follow-up. However, the risk remains high in successfully treated patients with low platelet count and in patients who did not achieve SVR with more adv
肝细胞癌(HCC)是全球癌症相关死亡的第二大常见原因，发病率不断上升。慢性丙型肝炎(CHC)的有效抗病毒治疗在过去7年中已经出现，但尽管世卫组织制定了消除肝炎的目标，但目前还没有在所有地区对所有患者普遍提供抗病毒治疗，这表明在未来几十年，慢性丙型肝炎相关HCC的前景仍然黯淡。目的评估来自单一机构的大型慢性丙型肝炎(CHC)患者的HCC发生率与干扰素(IFN)抗病毒治疗反应和基线特征的关系。方法回顾性收集1989年至2011年间诊断并在维也纳akh -大学医院接受直接抗病毒(DAA)治疗前接受治疗的CHC患者的资料。我们根据患者的基线特征分析了有持续病毒学反应(SVR)和没有SVR的患者的HCC发病率。结果本研究纳入了2134例患者，接受或未接受基于干扰素的抗病毒治疗，并进行了长期随访。该队列中HCC的总发病率为6.2%(在9年的中位随访期间有132例HCC)。根据基线纤维化分期，HCC总发病率为:基线纤维化F0-2期患者为1.1%，F3期为8.2%，F4期为20.6%。与SVR患者相比，非SVR组和未治疗组的HCC发生率显著高于SVR组:12.4% vs 1.9%， P <0001, 7.3% vs . 1.9%， P <在多变量分析中，SVR组较低的血小板计数(比值比OR = -0.1, 95% CI: 0.15-0.63)和非SVR组存在肝硬化(OR = 3.6, 95% CI: 1.59-8.17)、ALBI分级>=2 (OR = 2.3, 95% CI: 1.0-5.3)与HCC的发生独立相关。对于未接受治疗的患者组，HCC的唯一预测因子是高基线甲胎蛋白值(OR = 10.2, 95% CI: 2.2-47.9)。结论达到SVR可显著降低肝细胞癌的长期随访风险。然而，在治疗成功的低血小板计数患者和未达到SVR的晚期肝病患者中，风险仍然很高。这些危险因素应在本地区HCC监测决策中予以考虑。
{"title":"Hepatocellular carcinoma incidence in chronic hepatitis C patients according to sustained virological response (SVR) with interferon-based therapies and baseline characteristics","authors":"Tuul Purevsambuu, Simona Bota, Florian Hucke, Harald Hofer, Peter Ferenci, Wolfgang Sieghart, Markus Peck-Radosavljevic","doi":"10.1002/lci2.52","DOIUrl":"10.1002/lci2.52","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death worldwide with increasing incidence. Effective antiviral treatment for chronic hepatitis C (CHC) became available in the last 7 years but despite the WHO Hepatitis elimination targets, they are not universally available today in all regions for all the patients, indicating still a bleak outlook for CHC-associated HCC in the next decades.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To assess the HCC incidence in relation to interferon (IFN)-based antiviral treatment response and baseline characteristics of a large cohort of chronic hepatitis C (CHC) patients from a single institution.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively collected data of CHC patients, who were diagnosed between 1989 and 2011 and treated at the AKH-University Hospital of Vienna before the introduction of direct-acting antiviral (DAA) only therapy. We analysed the HCC incidence in patients with a sustained virological response (SVR) and without SVR according to the patients' baseline characteristics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our study included 2134 patients, who were treated or not treated with IFN-based antiviral treatment and had long-term follow-up available. The overall HCC incidence in this cohort was 6.2% (132 HCC cases over a median follow-up period of 9 years). According to the baseline fibrosis stage, the overall HCC incidence was: 1.1% in patients with baseline fibrosis stage F0-2, 8.2% in F3 and 20.6% in F4 patients. The HCC incidence was significantly higher in non-SVR and no-treatment group as compared with SVR patients: 12.4% vs 1.9%, <i>P</i> < .0001, 7.3% vs 1.9%, <i>P</i> < .0001. In multivariate analysis, lower platelet count (odds ratio-OR = -0.1, 95% CI: 0.15-0.63), for the SVR group and presence of cirrhosis (OR = 3.6, 95% CI: 1.59-8.17), ALBI grade >=2 (OR = 2.3, 95% CI: 1.0-5.3) for the non-SVR group were independently associated with HCC occurrence. For the group of patients with no treatment, the only predictor for HCC was high baseline alpha-fetoprotein values (OR = 10.2, 95% CI: 2.2-47.9).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The achievement of SVR significantly reduces the risk for HCC occurrence during long-term follow-up. However, the risk remains high in successfully treated patients with low platelet count and in patients who did not achieve SVR with more adv","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"3 2","pages":"53-62"},"PeriodicalIF":0.0,"publicationDate":"2022-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.52","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48941417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eleonora Di Carlo, Antonio D'Alessio, Antonella Cammarota, Valentina Zanuso, Tiziana Pressiani, Silvia Bozzarelli, Giuseppe Ferrillo, Giulia Vatteroni, Vittorio Pedicini, Laura Giordano, Nicola Personeni, Lorenza Rimassa
Background & Aims
Treatment of hepatocellular carcinoma (HCC) with immune checkpoint inhibitors (ICIs) is associated with the development of hepatic immune-related adverse events (HIRAEs). We aimed to evaluate the role of baseline hepatic tumour burden, measured with the tumour burden score (TBS), in the development of HIRAEs and survival.
Methods
We conducted a retrospective observational cohort study on 93 patients treated with ICIs at IRCCS Humanitas Research Hospital, of which 42 for advanced HCC (Cohort 1) and 51 for non-HCC cancers with liver metastases developed prior to immunotherapy initiation (Cohort 2). We assessed the baseline tumour burden using TBS: TBS2 = (maximum tumour diameter)2 + (number of liver lesions)2.
Results
In the cohort of patients with HCC, 18 patients (42.86%) developed any grade (G) HIRAEs, of which eight (19.05%) were G ≥ 2. Patients who developed any-grade HIRAEs had a higher median TBS compared to patients with no HIRAEs (10.95 vs 5.85; P = .11). Baseline TBS correlated with the development of any-grade HIRAEs with marginal statistical significance (odds ratio [OR] 1.37, P = .08). Median OS was not influenced by TBS or by the development of HIRAEs.
In the cohort of non-HCC patients, 18 patients (35.29%) developed any-grade HIRAEs, of which three (5.88%) were G ≥ 2. Baseline TBS did not correlate with the development of any-grade HIRAEs (OR 1.01), and median OS was not influenced by TBS or HIRAEs.
Conclusions
Despite the limited sample size and the absence of statistical significance, our study suggested a possible association between baseline TBS and the development of any-grade HIRAEs in the HCC cohort. Future evaluation of larger cohorts is needed to corroborate these findings.
背景,目的使用免疫检查点抑制剂(ICIs)治疗肝细胞癌(HCC)与肝脏免疫相关不良事件(hirae)的发生有关。我们的目的是评估基线肝肿瘤负荷的作用，用肿瘤负荷评分(TBS)来衡量，在HIRAEs的发展和生存中。我们对在IRCCS Humanitas研究医院接受ICIs治疗的93例患者进行了回顾性观察队列研究，其中42例为晚期HCC(队列1)，51例为在免疫治疗开始前发生肝转移的非HCC癌症(队列2)。我们使用TBS评估基线肿瘤负担:TBS2 =(最大肿瘤直径)2 +(肝脏病变数)2。结果HCC患者队列中，18例(42.86%)发生任何(G)级HIRAEs，其中8例(19.05%)为G≥2级。发生任何级别hiae的患者与未发生hiae的患者相比，TBS中位数更高(10.95 vs 5.85;p = .11)。基线TBS与任何级别hiae的发生相关，且具有边际统计学意义(优势比[OR] 1.37, P = .08)。中位OS不受TBS或HIRAEs的影响。在非hcc患者队列中，18例(35.29%)发生了任何级别的hirae，其中3例(5.88%)为G≥2。基线TBS与任何级别HIRAEs的发生均无相关性(OR 1.01)，中位OS不受TBS或HIRAEs的影响。尽管样本量有限且缺乏统计学意义，但我们的研究表明，基线TBS与HCC队列中任何级别hiae的发生之间可能存在关联。未来需要对更大的队列进行评估以证实这些发现。
{"title":"Tumour burden score and immune-related hepatotoxicity in patients with hepatocellular carcinoma or liver metastases treated with immune checkpoint inhibitors","authors":"Eleonora Di Carlo, Antonio D'Alessio, Antonella Cammarota, Valentina Zanuso, Tiziana Pressiani, Silvia Bozzarelli, Giuseppe Ferrillo, Giulia Vatteroni, Vittorio Pedicini, Laura Giordano, Nicola Personeni, Lorenza Rimassa","doi":"10.1002/lci2.51","DOIUrl":"10.1002/lci2.51","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background & Aims</h3>\u0000 \u0000 <p>Treatment of hepatocellular carcinoma (HCC) with immune checkpoint inhibitors (ICIs) is associated with the development of hepatic immune-related adverse events (HIRAEs). We aimed to evaluate the role of baseline hepatic tumour burden, measured with the tumour burden score (TBS), in the development of HIRAEs and survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective observational cohort study on 93 patients treated with ICIs at IRCCS Humanitas Research Hospital, of which 42 for advanced HCC (Cohort 1) and 51 for non-HCC cancers with liver metastases developed prior to immunotherapy initiation (Cohort 2). We assessed the baseline tumour burden using TBS: TBS<sup>2</sup> = (maximum tumour diameter)<sup>2</sup> + (number of liver lesions)<sup>2</sup>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the cohort of patients with HCC, 18 patients (42.86%) developed any grade (G) HIRAEs, of which eight (19.05%) were G ≥ 2. Patients who developed any-grade HIRAEs had a higher median TBS compared to patients with no HIRAEs (10.95 vs 5.85; <i>P</i> = .11). Baseline TBS correlated with the development of any-grade HIRAEs with marginal statistical significance (odds ratio [OR] 1.37, <i>P</i> = .08). Median OS was not influenced by TBS or by the development of HIRAEs.</p>\u0000 \u0000 <p>In the cohort of non-HCC patients, 18 patients (35.29%) developed any-grade HIRAEs, of which three (5.88%) were G ≥ 2. Baseline TBS did not correlate with the development of any-grade HIRAEs (OR 1.01), and median OS was not influenced by TBS or HIRAEs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Despite the limited sample size and the absence of statistical significance, our study suggested a possible association between baseline TBS and the development of any-grade HIRAEs in the HCC cohort. Future evaluation of larger cohorts is needed to corroborate these findings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"3 2","pages":"63-71"},"PeriodicalIF":0.0,"publicationDate":"2022-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.51","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41827309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Giacomo Aimar, Donatella Marino, Clizia Zichi, Teresa Gamba, Andrea Caglio, Francesca De Vita, Elisa Sperti, Massimo Di Maio
In the past years, treatment options for advanced hepatocellular carcinoma (HCC) have thriven. Although globally recognised, the patient-reported outcomes (PROs) are often underused and quality of life (QoL) results are underreported in many phase III trials. We performed a systematic review to describe the prevalence of QoL inclusion and heterogeneity in QoL reporting in published phase III trials of systemic treatment in advanced HCC. Twenty-one publications were identified: 12 (57.1%) in first line setting, eight (38.1%) in second line and only one (4.7%) in second and further lines. In 14 trials (66.6%), Qol was included in the analysis as a secondary or tertiary endpoint but only in nine (47.4%) cases Qol results were published in the main paper. QoL data are lacking in a significant proportion of published phase III trials in advanced HCC. The methodology of QoL analysis is heterogeneous for type of instruments, analysis and presentation of results.
{"title":"Advanced hepatocellular carcinoma: Impact of systemic treatments on health-related quality of life and patient-reported outcomes","authors":"Giacomo Aimar, Donatella Marino, Clizia Zichi, Teresa Gamba, Andrea Caglio, Francesca De Vita, Elisa Sperti, Massimo Di Maio","doi":"10.1002/lci2.50","DOIUrl":"10.1002/lci2.50","url":null,"abstract":"<p>In the past years, treatment options for advanced hepatocellular carcinoma (HCC) have thriven. Although globally recognised, the patient-reported outcomes (PROs) are often underused and quality of life (QoL) results are underreported in many phase III trials. We performed a systematic review to describe the prevalence of QoL inclusion and heterogeneity in QoL reporting in published phase III trials of systemic treatment in advanced HCC. Twenty-one publications were identified: 12 (57.1%) in first line setting, eight (38.1%) in second line and only one (4.7%) in second and further lines. In 14 trials (66.6%), Qol was included in the analysis as a secondary or tertiary endpoint but only in nine (47.4%) cases Qol results were published in the main paper. QoL data are lacking in a significant proportion of published phase III trials in advanced HCC. The methodology of QoL analysis is heterogeneous for type of instruments, analysis and presentation of results.</p>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"3 2","pages":"90-98"},"PeriodicalIF":0.0,"publicationDate":"2022-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.50","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46866386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shirin Nkongolo, Isabelle Mohr, Jürgen J. Wenzel, Dina Khalid, Markus Mieth, Arianeb Mehrabi, Karl Heinz Weiss, Paul Schnitzler
Background and Aims
Hepatitis E virus (HEV) is an increasingly recognised pathogen in industrialised countries, in particular genotype 3. Patients with underlying liver disease are at increased risk for severe course of the infection. Additionally, patients receiving immunosuppressive therapy can develop chronic HEV infection, which may cause further liver damage and ultimately lead to cirrhosis, decompensation or death.
Methods
This retrospective study assessed 1023 patients on the waiting list for liver transplantation, of which 636 were transplanted, for conducted HEV diagnostics, courses of disease and management, in the time from 2007 to 2018. Viral loads and HEV genotypes were determined retrospectively for selected cases.
Results
We found a seroprevalence of 29.7%. Forty-five patients (4.4%) seroconverted during the study period, indicating newly acquired infection. HEV replication was detected in nine patients (0.9%), seven of which were managed in our clinic and further analysed. Three of these patients were diagnosed with active HEV infection retrospectively. All patients with replicating HEV were liver-transplanted and therefore treated with immunosuppressants; four developed chronic infection >3 months. Two patients were also diagnosed with graft rejection when they had active hepatitis E. Patients who received antiviral treatment with Ribavirin cleared the infection and normalised alanine aminotransferase (ALT) levels within few weeks.
Conclusion
The results argue for more and systematic HEV testing of liver-transplanted patients, in routine settings and especially when ALT is elevated, as infections may be significantly underdiagnosed. Patients receiving immunosuppressive therapy who develop chronic infection can effectively be treated to prevent further liver damage.
{"title":"Hepatitis E seroprevalence, cases and management in a large German centre for liver transplantation","authors":"Shirin Nkongolo, Isabelle Mohr, Jürgen J. Wenzel, Dina Khalid, Markus Mieth, Arianeb Mehrabi, Karl Heinz Weiss, Paul Schnitzler","doi":"10.1002/lci2.48","DOIUrl":"10.1002/lci2.48","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Hepatitis E virus (HEV) is an increasingly recognised pathogen in industrialised countries, in particular genotype 3. Patients with underlying liver disease are at increased risk for severe course of the infection. Additionally, patients receiving immunosuppressive therapy can develop chronic HEV infection, which may cause further liver damage and ultimately lead to cirrhosis, decompensation or death.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study assessed 1023 patients on the waiting list for liver transplantation, of which 636 were transplanted, for conducted HEV diagnostics, courses of disease and management, in the time from 2007 to 2018. Viral loads and HEV genotypes were determined retrospectively for selected cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found a seroprevalence of 29.7%. Forty-five patients (4.4%) seroconverted during the study period, indicating newly acquired infection. HEV replication was detected in nine patients (0.9%), seven of which were managed in our clinic and further analysed. Three of these patients were diagnosed with active HEV infection retrospectively. All patients with replicating HEV were liver-transplanted and therefore treated with immunosuppressants; four developed chronic infection >3 months. Two patients were also diagnosed with graft rejection when they had active hepatitis E. Patients who received antiviral treatment with Ribavirin cleared the infection and normalised alanine aminotransferase (ALT) levels within few weeks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The results argue for more and systematic HEV testing of liver-transplanted patients, in routine settings and especially when ALT is elevated, as infections may be significantly underdiagnosed. Patients receiving immunosuppressive therapy who develop chronic infection can effectively be treated to prevent further liver damage.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"3 2","pages":"72-81"},"PeriodicalIF":0.0,"publicationDate":"2022-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.48","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45326777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alessandro Vitale, Silvia Caregari, Edoardo G. Giannini
The complexity of the evaluation of patients with hepatocellular carcinoma (HCC) is related to the need of simultaneously considering – when planning treatment and assessing prognosis – not only the magnitude of tumour burden and the degree of general well-being of patients (i.e. their Performance Status [PS]) as in other malignancies, but also the extent of the concomitant liver dysfunction. Moreover, adding further complications to the difficulties faced in streamlining this complex process, various evidence-based treatments are available to treat patients with HCC. This has led, through the years, to the development of several, variously designed prognostic scores and staging systems, without having yet reached a consensus on the universally accepted best one.
HCC prognostic assessment scores can be divided into two main categories, differing in design characteristics (data based or evidence based), prognostic value, significance in treatment allocation.1 Evidence-based staging systems (Tumour Nodes Metastasis [TNM], Barcelona Clinic Liver Cancer [BCLC] and Chinese Liver Cancer [CNLC] classifications) are defined based on HCC patients' prognostic evidence from the literature and typically offer a linkage, sometimes univocal, with treatment modalities. Data-based prognostic scores (Okuda staging system, Cancer of the Liver Italian Program [CLIP] score, Japan Integrated Staging [JIS] score, Model to Estimate Survival for HCC [MESH] score], on the other hand, are obtained with rigorous statistical methodology and demonstrated to have a better prognostic performance compared to evidence-based staging systems.2 Lastly, a third category can also be identified, namely combined prognostic systems, used both as prognostic scores and staging systems. A recent example of one of these systems, based on literature evidence but weighted in a real population, is the Italian Liver Cancer (ITA.LI.CA) prognostic system.3
The Hepatocellular Carcinoma Survival Prediction Score (HCC-SPS), proposed by Tan et al. in the current issue of Liver Cancer International, can be categorised as a data-based prognostic score. Indeed, this study is an interesting example of how this kind of scores are created, relying on real-life population data, solid statistical bases, internal and external validation.4 Noteworthy, the HCC-SPS score incorporates a multitude of parameters in comparison with other HCC survival scores. In addition to tumour characteristics, it also assesses liver functional reserve, the albumin–bilirubin (ALBI) grade and patient's physical functional status. Furthermore, it includes the only humoral parameter which is widely available in clinical practice to assess the ‘biological aggressiveness’ of HCC, such as alpha-fetoprotein.5 One of its limits, though, is the scarce numerosity of the external validation populations.
{"title":"Need for independence of treatment allocation from prognostic evaluation for hepatocellular carcinoma","authors":"Alessandro Vitale, Silvia Caregari, Edoardo G. Giannini","doi":"10.1002/lci2.49","DOIUrl":"10.1002/lci2.49","url":null,"abstract":"<p>The complexity of the evaluation of patients with hepatocellular carcinoma (HCC) is related to the need of simultaneously considering – when planning treatment and assessing prognosis – not only the magnitude of tumour burden and the degree of general well-being of patients (i.e. their Performance Status [PS]) as in other malignancies, but also the extent of the concomitant liver dysfunction. Moreover, adding further complications to the difficulties faced in streamlining this complex process, various evidence-based treatments are available to treat patients with HCC. This has led, through the years, to the development of several, variously designed prognostic scores and staging systems, without having yet reached a consensus on the universally accepted best one.</p><p>HCC prognostic assessment scores can be divided into two main categories, differing in design characteristics (data based or evidence based), prognostic value, significance in treatment allocation.<span><sup>1</sup></span> Evidence-based staging systems (Tumour Nodes Metastasis [TNM], Barcelona Clinic Liver Cancer [BCLC] and Chinese Liver Cancer [CNLC] classifications) are defined based on HCC patients' prognostic evidence from the literature and typically offer a linkage, sometimes univocal, with treatment modalities. Data-based prognostic scores (Okuda staging system, Cancer of the Liver Italian Program [CLIP] score, Japan Integrated Staging [JIS] score, Model to Estimate Survival for HCC [MESH] score], on the other hand, are obtained with rigorous statistical methodology and demonstrated to have a better prognostic performance compared to evidence-based staging systems.<span><sup>2</sup></span> Lastly, a third category can also be identified, namely combined prognostic systems, used both as prognostic scores and staging systems. A recent example of one of these systems, based on literature evidence but weighted in a real population, is the Italian Liver Cancer (ITA.LI.CA) prognostic system.<span><sup>3</sup></span></p><p>The Hepatocellular Carcinoma Survival Prediction Score (HCC-SPS), proposed by Tan et al. in the current issue of Liver Cancer International, can be categorised as a data-based prognostic score. Indeed, this study is an interesting example of how this kind of scores are created, relying on real-life population data, solid statistical bases, internal and external validation.<span><sup>4</sup></span> Noteworthy, the HCC-SPS score incorporates a multitude of parameters in comparison with other HCC survival scores. In addition to tumour characteristics, it also assesses liver functional reserve, the albumin–bilirubin (ALBI) grade and patient's physical functional status. Furthermore, it includes the only humoral parameter which is widely available in clinical practice to assess the ‘biological aggressiveness’ of HCC, such as alpha-fetoprotein.<span><sup>5</sup></span> One of its limits, though, is the scarce numerosity of the external validation populations.</p><p","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"3 2","pages":"51-52"},"PeriodicalIF":0.0,"publicationDate":"2022-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.49","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43207214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ken Liu, Terry C. F. Yip, Steven Masson, Waleed Fateen, Tae-Hwi Schwantes-An, Geoffrey W. McCaughan, Timothy R. Morgan, Guruprasad P. Aithal, Devanshi Seth
Background and Aims
The aMAP score was recently devised to predict hepatocellular carcinoma (HCC) development. However, its performance was not tested in alcohol-related cirrhosis (ALC). We aimed to validate the aMAP score in a cohort of ALC patients.
Method
Study participants with ALC from a prior genome-wide association study were included. All participants had a history of high alcohol consumption. Cirrhosis was defined clinically, using fibroscan and/or histology. Patients were followed until the last liver imaging, HCC, liver transplantation (LT) or death with the latter two adjusted as competing risks.
Results
A total of 269 ALC patients were included: male (72.5%), Caucasian (98.9%), median age 56 years, and median Child-Pugh score 7. The median aMAP score was 60: 12.3% low-risk, 35.3% medium-risk and 52.4% high-risk. After a median follow-up of 41 months, 14 patients developed HCC, 27 received LT and 104 died. The aMAP score predicted HCC development (hazard ratio 1.12 per point increase, P < .001) with good separation of cumulative incidence function between risk groups. The area under the time-dependent receiver operating characteristics curve for predicting HCC development was 0.83 at 1 year and 0.82 at 5 years which was similar to ADRESS-HCC and Veterans Affairs Healthcare System scores respectively.
Conclusions
We validated the excellent performance of the aMAP score in ALC and affirm its applicability across wider aetiologies.
{"title":"Validation of the aMAP score to predict hepatocellular carcinoma development in a cohort of alcohol-related cirrhosis patients","authors":"Ken Liu, Terry C. F. Yip, Steven Masson, Waleed Fateen, Tae-Hwi Schwantes-An, Geoffrey W. McCaughan, Timothy R. Morgan, Guruprasad P. Aithal, Devanshi Seth","doi":"10.1002/lci2.47","DOIUrl":"10.1002/lci2.47","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>The aMAP score was recently devised to predict hepatocellular carcinoma (HCC) development. However, its performance was not tested in alcohol-related cirrhosis (ALC). We aimed to validate the aMAP score in a cohort of ALC patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>Study participants with ALC from a prior genome-wide association study were included. All participants had a history of high alcohol consumption. Cirrhosis was defined clinically, using fibroscan and/or histology. Patients were followed until the last liver imaging, HCC, liver transplantation (LT) or death with the latter two adjusted as competing risks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 269 ALC patients were included: male (72.5%), Caucasian (98.9%), median age 56 years, and median Child-Pugh score 7. The median aMAP score was 60: 12.3% low-risk, 35.3% medium-risk and 52.4% high-risk. After a median follow-up of 41 months, 14 patients developed HCC, 27 received LT and 104 died. The aMAP score predicted HCC development (hazard ratio 1.12 per point increase, <i>P</i> < .001) with good separation of cumulative incidence function between risk groups. The area under the time-dependent receiver operating characteristics curve for predicting HCC development was 0.83 at 1 year and 0.82 at 5 years which was similar to ADRESS-HCC and Veterans Affairs Healthcare System scores respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We validated the excellent performance of the aMAP score in ALC and affirm its applicability across wider aetiologies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"3 2","pages":"99-104"},"PeriodicalIF":0.0,"publicationDate":"2022-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.47","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41821684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Terence J.Y. Tan, Liang Shen, Saur Hajiev, Lung-Yi Mak, Rohini Sharma, George B.B. Goh, Pik-Eu Chang, Man-Fung Yuen, David J. Pinato, Chee-Kiat Tan
Background & Aims
Survival in hepatocellular carcinoma (HCC) is associated with several factors. Our aim was to develop and validate an HCC survival prediction score (HCC-SPS) based on common clinical parameters and excluding the subsequent therapy received, which would be able to prognosticate all patients with HCC at the time of diagnosis.
Methods
The development cohort comprised 1270 patients with HCC seen in our department since January 1988. Univariate analysis was performed for known HCC prognostic parameters. Parameters with P < .1 on univariate analysis were then included in a Cox regression with backward model selection. The HCC-SPS was derived based on the coefficients estimated by Cox regression with selected parameters. The derived HCC-SPS was then validated with 2 independent international cohorts of 220 patients from the United Kingdom and 90 patients from Hong Kong (HK). Points were allocated to the following variables: ALBI grade, AFP level, portal vein invasion, ECOG status and TNM stage.
Results
The total score classified a patient into 3 distinct survival risk categories of low, medium and high risk with median survival (weeks) of 249 (95% CI 195–303), 45 (95% CI 38–52) and 9 (95% CI 8–10) respectively. The scoring system was validated by the cohorts from United Kingdom and HK.
Conclusions
We have formulated an HCC survival prediction score using readily available clinical parameters to risk stratify all HCC patients into distinct survival categories at the time of HCC diagnosis regardless of subsequent treatment received. The score was validated with other independent international cohorts of patients.
背景,目的肝细胞癌(HCC)患者的生存与多种因素相关。我们的目的是开发和验证HCC生存预测评分(HCC- sps)，该评分基于常见的临床参数，不包括随后接受的治疗，能够在诊断时预测所有HCC患者。方法回顾性分析1988年1月以来我科收治的1270例肝癌患者。对已知的HCC预后参数进行单因素分析。参数带P <.1的单因素分析，然后纳入Cox回归与逆向模型选择。采用Cox回归法对各参数进行系数估计，得到HCC-SPS。然后用来自英国的220名患者和来自香港的90名患者的2个独立国际队列验证了衍生的HCC-SPS。对ALBI分级、AFP水平、门静脉侵犯、ECOG状态、TNM分期进行评分。结果总评分将患者分为低、中、高风险3个不同的生存风险类别，中位生存期(周)分别为249 (95% CI 195 ~ 303)、45 (95% CI 38 ~ 52)和9 (95% CI 8 ~ 10)。来自英国和香港的队列验证了评分系统。我们已经制定了一个HCC生存预测评分，使用现成的临床参数，将所有HCC患者在HCC诊断时分为不同的生存类别，而不管随后接受了什么治疗。该评分通过其他独立的国际患者队列进行验证。
{"title":"Development and validation of a therapy-independent hepatocellular carcinoma survival prediction score","authors":"Terence J.Y. Tan, Liang Shen, Saur Hajiev, Lung-Yi Mak, Rohini Sharma, George B.B. Goh, Pik-Eu Chang, Man-Fung Yuen, David J. Pinato, Chee-Kiat Tan","doi":"10.1002/lci2.45","DOIUrl":"10.1002/lci2.45","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background & Aims</h3>\u0000 \u0000 <p>Survival in hepatocellular carcinoma (HCC) is associated with several factors. Our aim was to develop and validate an HCC survival prediction score (HCC-SPS) based on common clinical parameters and excluding the subsequent therapy received, which would be able to prognosticate all patients with HCC at the time of diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The development cohort comprised 1270 patients with HCC seen in our department since January 1988. Univariate analysis was performed for known HCC prognostic parameters. Parameters with <i>P</i> < .1 on univariate analysis were then included in a Cox regression with backward model selection. The HCC-SPS was derived based on the coefficients estimated by Cox regression with selected parameters. The derived HCC-SPS was then validated with 2 independent international cohorts of 220 patients from the United Kingdom and 90 patients from Hong Kong (HK). Points were allocated to the following variables: ALBI grade, AFP level, portal vein invasion, ECOG status and TNM stage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The total score classified a patient into 3 distinct survival risk categories of low, medium and high risk with median survival (weeks) of 249 (95% CI 195–303), 45 (95% CI 38–52) and 9 (95% CI 8–10) respectively. The scoring system was validated by the cohorts from United Kingdom and HK.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We have formulated an HCC survival prediction score using readily available clinical parameters to risk stratify all HCC patients into distinct survival categories at the time of HCC diagnosis regardless of subsequent treatment received. The score was validated with other independent international cohorts of patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"3 2","pages":"82-89"},"PeriodicalIF":0.0,"publicationDate":"2022-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.45","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42782300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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