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1
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Kokudo T, Kokudo N. Impact of hepatitis C virus infection control on preventing the postoperative recurrence of intrahepatic cholangiocarcinoma. Hepatol Res 2025; 55:629-630. [PMID: 40318092 DOI: 10.1111/hepr.14182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/07/2025]
Affiliation(s)
- Takashi Kokudo
- National Center for Global Health and Medicine, Tokyo, Japan
| | - Norihiro Kokudo
- National Center for Global Health and Medicine, Tokyo, Japan
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Park W, Lee SK, Gwack J, Lee SY, Cho YG, Kang SB, Park J. Dysbiosis of Bile Microbiota in Cholangiocarcinoma Patients: A Comparison with Benign Biliary Diseases. Int J Mol Sci 2025; 26:1577. [PMID: 40004041 PMCID: PMC11855699 DOI: 10.3390/ijms26041577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 02/10/2025] [Accepted: 02/10/2025] [Indexed: 02/27/2025] Open
Abstract
Dysbiosis in the bile microbiota of cholangiocarcinoma (CCA) patients suggests a potential role for microbial alterations in the pathogenesis of CCA. This study aimed to investigate bile microbial communities in patients with CCA and compare them to those in individuals with benign biliary diseases as a control (CTR) group. Microbial profiling was conducted using next-generation sequencing (NGS), targeting the V3-V4 regions of the 16S rRNA gene, followed by bioinformatics analysis using the VSEARCH and EzBioCloud platforms. Alpha and beta diversity analyses were performed to assess microbial richness and structural differences. The linear discriminant analysis effect size (LEfSe) was utilized to identify potential microbial biomarkers. Results: This study identified distinct microbial profiles in the two groups at both the phylum and genus levels. In the CTR group, Pseudomonadota (65%) was the dominant phyla, while Bacillota (49%) was more abundant in the CCA group. At the genus level, Escherichia (29%), Enterobacteriaceae (12%), Enterococcus (8%), Ralstonia (8%), and Clostridium (5%) were more prevalent in the CTR group, whereas Streptococcus (34%), Ralstonia (8%), and Veillonella (5%) were dominant in the CCA group. Although an alpha diversity analysis showed no statistically significant differences in species richness or diversity between groups, a beta diversity analysis revealed significant structural differences associated with disease severity. Our comparative microbiome study using LEfSe analysis suggested a statistically significant inhibition of normal intestinal bacterial flora in patients with CCA who had not received any treatment. These findings suggest that microbial dysbiosis may play a role in the pathogenesis of CCA. Specific microbial taxa were identified as potential biomarkers for distinguishing benign from malignant diseases. These results underscore the potential role of microbial dysbiosis in CCA pathogenesis and highlight the bile microbiota's utility as a diagnostic marker for biliary diseases.
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Affiliation(s)
- Wonsuk Park
- Division of Gastroenterology, Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea;
| | - Sang Kuon Lee
- Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea;
| | - Jin Gwack
- Department of Prevention Medicine, College of Medicine, Jeonbuk National University, Jeonju 54907, Republic of Korea;
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea; (S.Y.L.); (Y.G.C.)
| | - Seung Yeob Lee
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea; (S.Y.L.); (Y.G.C.)
- Department of Laboratory Medicine, Jeonbuk National University College of Medicine and Hospital, Jeonju 54907, Republic of Korea
| | - Yong Gon Cho
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea; (S.Y.L.); (Y.G.C.)
- Department of Laboratory Medicine, Jeonbuk National University College of Medicine and Hospital, Jeonju 54907, Republic of Korea
| | - Sang-Bum Kang
- Division of Gastroenterology, Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea;
| | - Joonhong Park
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea; (S.Y.L.); (Y.G.C.)
- Department of Laboratory Medicine, Jeonbuk National University College of Medicine and Hospital, Jeonju 54907, Republic of Korea
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Tertiary Prevention of HCC in Chronic Hepatitis B or C Infected Patients. Cancers (Basel) 2021; 13:cancers13071729. [PMID: 33917345 PMCID: PMC8038691 DOI: 10.3390/cancers13071729] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 03/29/2021] [Accepted: 03/29/2021] [Indexed: 01/27/2023] Open
Abstract
Simple Summary Hepatocellular carcinoma (HCC) recurrence is the major obstacle concerning patients’ survival. Tertiary prevention by antiviral therapies could reduce HCC recurrence rate in both chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infected patients. In chronic hepatitis B (CHB) patients, nucleos(t)ide analogues (Nuc) provide a more effective HCC tertiary prevention effect than an interferon (IFN)-based regimen. In chronic hepatitis C (CHC) patients, the tertiary prevention effect by direct acting antiviral agents (DAAs) was reported non-inferior to that by IFN-based therapy. Chronic hepatitis C patients left untreated had the worst survival benefit as well as shorted recurrence-free interval than those treated by either type of antiviral regimen. Although the risk of HCC recurrence could only be decreased but not diminished by antiviral therapies due to host and microenvironmental factors beyond virus infection, antiviral therapy helps to preserve and improve liver function which makes multi-modality anticancer treatment feasible to improve survival. Abstract Hepatocellular carcinoma (HCC) ranks as a leading cause of common cancer and cancer-related death. The major etiology of HCC is due to chronic hepatitis virus including HBV and HCV infections. Scheduled HCC surveillance in high risk populations improves the early detection rate and the feasibility of curative treatment. However, high HCC recurrence rate still accounts for the poor prognosis of HCC patients. In this article, we critically review the pathogenesis of viral hepatitis-related hepatocellular carcinoma and the evidence of tertiary prevention efficacy by current available antiviral treatment, and discuss the knowledge gap in viral hepatitis-related HCC tertiary prevention.
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Wang JH, Li WF, Yong CC, Liu YW, Lu SN, Wang CC. Liver stiffness and insulin resistance in predicting recurrence for early stage hepatoma patients after curative resection. Sci Rep 2021; 11:6041. [PMID: 33723365 PMCID: PMC7961050 DOI: 10.1038/s41598-021-85431-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Accepted: 02/28/2021] [Indexed: 02/08/2023] Open
Abstract
Curative resection is recommended for patient with early stage hepatocellular carcinoma (HCC), however, the prognosis is limited by high recurrence rate. This study was to investigate liver stiffness (LS) and metabolic factor in prediction of HCC recurrence for patients with early stage HCC who had undergone curative resection. Consecutive patients with suspicion of HCC who had undergone curative resection were prospectively enrolled. Transient elastography was performed to determine LS pre-operatively. The demographics, clinical characteristics and histological findings were recorded. All patients were followed up regularly until recurrence, death or last visit. Ninety-four patients with early stage HCC were enrolled. LS positively correlated with fibrosis stage (r = 0.666). In a median follow-up of 3.2 years, forty patients developed recurrences including 22 recurrences after 1-year post resection. The 5-year cumulative recurrence rate was 44.2%. LS was the independent factor associated with recurrence. Patients with LS > 8.5 kPa had higher 5-year cumulative recurrence rate (59.8% vs 25.1%, p = 0.007). For the prediction of recurrence after 1-year post resection, LS > 8.5 kPa (hazard ratio 2.72) and homeostatic model assessment for insulin resistance index (HOMA-IR) (hazard ratio 1.24) were independent factors in multivariate analysis. Those patients with both LS > 8.5 kPa and HOMA-IR > 2.3 had the highest recurrence rate after 1-year post resection.
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Affiliation(s)
- Jing-Houng Wang
- Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung City, Taiwan
| | - Wei-Feng Li
- Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123, Ta Pei Road, Niao Sung 833, Kaohsiung City, Taiwan
| | - Chee-Chien Yong
- Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123, Ta Pei Road, Niao Sung 833, Kaohsiung City, Taiwan
| | - Yueh-Wei Liu
- Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123, Ta Pei Road, Niao Sung 833, Kaohsiung City, Taiwan
| | - Sheng-Nan Lu
- Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung City, Taiwan
| | - Chih-Chi Wang
- Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123, Ta Pei Road, Niao Sung 833, Kaohsiung City, Taiwan.
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Kwan BS, Kim JH, Park SJ, Choe WH, Kwon SY, Yoo BC. Comparison of the efficacy and safety of direct-acting antiviral therapy with or without hepatitis C-related hepatocellular carcinoma. Korean J Intern Med 2021; 36:292-304. [PMID: 32241083 PMCID: PMC7969069 DOI: 10.3904/kjim.2019.297] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 10/24/2019] [Accepted: 11/24/2019] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND/AIMS Chronic hepatitis C (CHC) treatment has dramatically improved since direct-acting antiviral (DAA) therapy was introduced. However, the use of DAA therapy in CHC patients with hepatocellular carcinoma (HCC) remains controversial. We investigated the DAA treatment response in CHC patients with HCC. METHODS We retrospectively analyzed CHC patients treated with DAA from 2016 to 2018. Patients were divided into two groups based on their HCC-history before DAA therapy. Baseline characteristics, sustained virologic response at 12 weeks (SVR 12), and HCC recurrence after DAA therapy were evaluated. We also used propensity score matching (PSM) in a 2:1 ratio to reduce confounding variables. RESULTS A total of 192 patients were enrolled; 78.1% were treatment-naïve, and 34.9% had liver cirrhosis (LC). Among these patients, 168 did not have HCC, and 24 had HCC. The HCC group was older (57.0 years vs. 72.0 years, p < 0.001), had a higher incidence of LC (26.2% vs. 95.8%, p < 0.001), fibrosis-4 index (2.6 vs. 9.2, p < 0.001), liver stiffness measurement (7.0 kPa vs. 17.4 kPa, p = 0.012), and α-fetoprotein (4.4 ng/mL vs. 8.2 ng/mL, p ≤ 0.001). The SVR 12 rate was 97.0% in the non- HCC group and 91.7% in the HCC group (p = 0.213). HCC recurrence was observed in 14 patients (58.3%) in the HCC group. CONCLUSION DAA treatment efficacy in CHC patients with or those without HCC were not significantly different, and HCC recurrence was relatively common.
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Affiliation(s)
- Byung Soo Kwan
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Jeong Han Kim
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
- Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Korea
| | - Seong Jun Park
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Won Hyeok Choe
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - So Young Kwon
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Byung-Chul Yoo
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
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Wang P, Shen Y, Zhao L. Chitosan nanoparticles loaded with aspirin and 5-fluororacil enable synergistic antitumour activity through the modulation of NF-κB/COX-2 signalling pathway. IET Nanobiotechnol 2021; 14:479-484. [PMID: 32755957 DOI: 10.1049/iet-nbt.2020.0002] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Based on the enhancement of synergistic antitumour activity to treat cancer and the correlation between inflammation and carcinogenesis, the authors designed chitosan nanoparticles for co-delivery of 5-fluororacil (5-Fu: an as anti-cancer drug) and aspirin (a non-steroidal anti-inflammatory drug) and induced synergistic antitumour activity through the modulation of the nuclear factor kappa B (NF-κB)/cyclooxygenase-2 (COX-2) signalling pathways. The results showed that aspirin at non-cytotoxic concentrations synergistically sensitised hepatocellular carcinoma cells to 5-Fu in vitro. It demonstrated that aspirin inhibited NF-κB activation and suppressed NF-κB regulated COX-2 expression and prostaglandin E2 (PGE2) synthesis. Furthermore, the proposed results clearly indicated that the combination of 5-Fu and aspirin by chitosan nanoparticles enhanced the intracellular concentration of drugs and exerted synergistic growth inhibition and apoptosis induction on hepatocellular carcinoma cells by suppressing NF-κB activation and inhibition of expression of COX-2.
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Affiliation(s)
- Peng Wang
- Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, People's Republic of China
| | - Yaping Shen
- School of Pharmacy, Jinzhou Medical University, Jinzhou 121000, People's Republic of China
| | - Liang Zhao
- School of Pharmacy, Jinzhou Medical University, Jinzhou 121000, People's Republic of China.
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Chen P, Yang H, Chou C, Chang L, Hsu M, Tsai T, Fang C, Su C, Lin Y, Feng Y, Chen C. The effectiveness and safety of sofosbuvir‐ledipasvir for patients with hepatitis C virus genotype 2 infection. ADVANCES IN DIGESTIVE MEDICINE 2021. [DOI: 10.1002/aid2.13258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- Po‐Yueh Chen
- Department of Internal Medicine Ditmanson Medical Foundation Chia‐Yi Christian Hospital Chiayi Taiwan
| | - Hsin‐Yi Yang
- Clinical Medicine Research Center Ditmanson Medical Foundation Chia‐Yi Christian Hospital Chiayi Taiwan
| | - Chu‐Kuang Chou
- Department of Internal Medicine Ditmanson Medical Foundation Chia‐Yi Christian Hospital Chiayi Taiwan
| | - Li‐Jen Chang
- Department of Internal Medicine Ditmanson Medical Foundation Chia‐Yi Christian Hospital Chiayi Taiwan
| | - Ming‐Tse Hsu
- Department of Internal Medicine Ditmanson Medical Foundation Chia‐Yi Christian Hospital Chiayi Taiwan
| | - Tsung‐Jung Tsai
- Department of Internal Medicine Ditmanson Medical Foundation Chia‐Yi Christian Hospital Chiayi Taiwan
| | - Chien‐Chung Fang
- Department of Internal Medicine Ditmanson Medical Foundation Chia‐Yi Christian Hospital Chiayi Taiwan
| | - Chang‐Chao Su
- Department of Internal Medicine Ditmanson Medical Foundation Chia‐Yi Christian Hospital Chiayi Taiwan
| | - Yu‐Ling Lin
- Department of Internal Medicine Ditmanson Medical Foundation Chia‐Yi Christian Hospital Chiayi Taiwan
| | - Yu‐Ming Feng
- Department of Internal Medicine Ditmanson Medical Foundation Chia‐Yi Christian Hospital Chiayi Taiwan
| | - Chi‐Yi Chen
- Department of Internal Medicine Ditmanson Medical Foundation Chia‐Yi Christian Hospital Chiayi Taiwan
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Facciorusso A, Abd El Aziz MA, Cincione I, Cea UV, Germini A, Granieri S, Cotsoglou C, Sacco R. Angiotensin Receptor 1 Blockers Prolong Time to Recurrence after Radiofrequency Ablation in Hepatocellular Carcinoma patients: A Retrospective Study. Biomedicines 2020; 8:399. [PMID: 33050084 PMCID: PMC7599746 DOI: 10.3390/biomedicines8100399] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 10/04/2020] [Accepted: 10/06/2020] [Indexed: 02/07/2023] Open
Abstract
Inhibition of angiotensin II synthesis seems to decrease hepatocellular carcinoma recurrence after radical therapies; however, data on the adjuvant role of angiotensin II receptor 1 blockers (sartans) are still lacking. Aim of the study was to evaluate whether sartans delay time to recurrence and prolong overall survival in hepatocellular carcinoma patients after radiofrequency ablation. Data on 215 patients were reviewed. The study population was classified into three groups: 113 (52.5%) patients who received neither angiotensin-converting enzyme inhibitors nor sartans (group 1), 59 (27.4%) patients treated with angiotensin-converting enzyme inhibitors (group 2) and 43 (20.1%) patients treated with sartans (group 3). Survival outcomes were analyzed using Kaplan-Meier analysis and compared with log-rank test. In the whole study population, 85.6% of patients were in Child-Pugh A-class and 89.6% in Barcelona Clinic Liver Cancer A stage. Median maximum tumor diameter was 30 mm (10-40 mm) and alpha-fetoprotein was 25 (1.1-2100) IU/mL. No differences in baseline characteristics among the three groups were reported. Median overall survival was 48 months (42-51) in group 1, 51 months (42-88) in group 2, and 63 months (51-84) in group 3 (p = 0.15). Child-Pugh stage and Model for End-staging Liver Disease (MELD) score resulted as significant predictors of overall survival in multivariate analysis. Median time to recurrence was 33 months (24-35) in group 1, 41 (23-72) in group 2 and 51 months (42-88) in group 3 (p = 0.001). Number of nodules and anti-angiotensin treatment were confirmed as significant predictors of time to recurrence in multivariate analysis. Sartans significantly improved time to recurrence after radiofrequency ablation in hepatocellular carcinoma patients but did not improve overall survival.
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Affiliation(s)
- Antonio Facciorusso
- Department of Medical Sciences, Gastroenterology Unit, Ospedali Riuniti di Foggia, 71122 Foggia, Italy; (U.V.C.); (R.S.)
| | | | - Ivan Cincione
- Department of Clinical and Experimental Medicine, Faculty of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy;
| | - Ugo Vittorio Cea
- Department of Medical Sciences, Gastroenterology Unit, Ospedali Riuniti di Foggia, 71122 Foggia, Italy; (U.V.C.); (R.S.)
| | - Alessandro Germini
- General Surgery Department, ASST-Vimercate, 20871 Vimercate, Italy; (A.G.); (S.G.); (C.C.)
| | - Stefano Granieri
- General Surgery Department, ASST-Vimercate, 20871 Vimercate, Italy; (A.G.); (S.G.); (C.C.)
| | - Christian Cotsoglou
- General Surgery Department, ASST-Vimercate, 20871 Vimercate, Italy; (A.G.); (S.G.); (C.C.)
| | - Rodolfo Sacco
- Department of Medical Sciences, Gastroenterology Unit, Ospedali Riuniti di Foggia, 71122 Foggia, Italy; (U.V.C.); (R.S.)
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Ji Y, Chen H, Gow W, Ma L, Jin Y, Hui B, Yang Z, Wang Z. Potential biomarkers Ang II/AT1R and S1P/S1PR1 predict the prognosis of hepatocellular carcinoma. Oncol Lett 2020; 20:208. [PMID: 32963614 PMCID: PMC7491028 DOI: 10.3892/ol.2020.12071] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Accepted: 07/07/2020] [Indexed: 12/14/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the major causes of cancer-associated morbidity and mortality worldwide. Sphingosine-1-phosphate (S1P) and S1P receptor 1 (S1PR1) have been associated with the development and progression of HCC. Angiotensin II (Ang II) and Ang II receptor type 1 (AT1R) serve key roles in the progression and metastasis of HCC. However, the association and roles of Ang II/AT1R and S1P/S1PR1 in HCC have remained elusive. Therefore, the aim of the present study was to investigate the potential association between Ang II/AT1R and S1P/S1PR1 in HCC, as well as the association of AT1R and S1PR1 protein expression levels with the progression and prognosis of HCC. The results found that the serum levels of Ang II and S1P were significantly higher in patients with HCC compared with those in healthy donors. Furthermore, mRNA and protein levels of AT1R and S1PR1 were highly expressed in human HCC tissues. In addition, a positive correlation between Ang II/S1P and AT1R/S1PR1 in HCC was noted. Upregulation of AT1R and S1PR1 was associated with the progression of HCC. Patients with high AT1R and S1PR1 protein expression levels had unfavorable outcomes with respect to overall survival and recurrence-free survival compared with patients with low AT1R and S1PR1 expression levels. The present results demonstrated an association between AT1R and S1PR1 overexpression and the progression of HCC, indicating that Ang II/AT1R and S1P/S1PR may serve as valuable prognostic biomarkers for HCC.
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Affiliation(s)
- Yuanyuan Ji
- Scientific Research Center and Precision Medical Institute, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
| | - Haiyan Chen
- Scientific Research Center and Precision Medical Institute, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
| | - Wei Gow
- Basic Medical Experiment Teaching Center, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Li Ma
- Department of Pathology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
| | - Yaofeng Jin
- Department of Pathology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
| | - Bo Hui
- Department of General Surgery, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
| | - Zhengan Yang
- Department of General Surgery, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
| | - Zhidong Wang
- Department of General Surgery, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
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Asahina Y. JSH Guidelines for the Management of Hepatitis C Virus Infection, 2019 Update; Protective Effect of Antiviral Therapy against Hepatocarcinogenesis. Hepatol Res 2020; 50:775-790. [PMID: 32298527 DOI: 10.1111/hepr.13501] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 03/04/2020] [Accepted: 04/05/2020] [Indexed: 02/08/2023]
Abstract
The Drafting Committee for Hepatitis Management Guidelines established by the Japan Society of Hepatology (JSH) drafted the first version of the clinical practice guidelines for the management of hepatitis C virus (HCV) infection in 2012. Since then, we have been publishing updates as new drugs for hepatitis C become available and new indications for existing drugs are added. The new approval of sofosbuvir/velpatasvir prompted us to publish the seventh version of the guidelines in Japanese in March 2019. We also published the first English-language version of the JSH guidelines in 2013 and English versions of updates made to the Japanese-language guidelines in 2014 and 2016. In 2020, the committee has decided to publish a new English version, covering general information about treatment for hepatitis C, drugs used, recommended treatments for chronic hepatitis and cirrhosis, and special populations, such as patients who have renal impairment, are on dialysis, or have developed recurrence of hepatitis C after liver transplantation. Furthermore, the committee has released a separate publication covering the protective effect of antiviral therapy against hepatocarcinogenesis.
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Sheu MJ, Liang FW, Li ST, Li CY, Lu TH. Validity of ICD-10-CM Codes Used to Identify Patients with Chronic Hepatitis B and C Virus Infection in Administrative Claims Data from the Taiwan National Health Insurance Outpatient Claims Dataset. Clin Epidemiol 2020; 12:185-192. [PMID: 32110110 PMCID: PMC7039074 DOI: 10.2147/clep.s236823] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Accepted: 02/02/2020] [Indexed: 12/20/2022] Open
Abstract
PURPOSE To validate the use of International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes to identify patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in the Taiwan National Health Insurance (NHI) Outpatient Claims Dataset. METHODS We conducted a retrospective study using results of HBV surface antigen (HBsAg), HBV e antigen (HBeAg), and anti-HCV antibody tests in the NHI Lab & Exam Dataset from January 1 to March 31, 2018, as the reference standard to confirm HBV and HCV infection cases. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) to assess the performance of HBV infection-specific ICD-10-CM codes (B180, B181, and B191) and HCV infection-specific ICD-10-CM codes (B182 and B192) recorded in the NHI Outpatient Claims Dataset to identify patients with HBV or HCV infection. RESULTS In total, 196,635 and 120,628 patients had analyzable results for HBsAg/HBeAg tests and anti-HCV tests, respectively. Moreover, 44,574 and 14,443 were confirmed to have HBV and HCV infection, respectively. The sensitivity, specificity, PPV, and NPV were, respectively, 46%, 83%, 45%, and 84% for HBV infection-specific ICD-10-CM codes and 47%, 99%, 81%, and 93% for HCV infection-specific ICD-10-CM codes. The sensitivity demonstrated great variation by region, clinical setting, and physician specialty. CONCLUSION The HBV and HCV infection-specific ICD-10-CM codes recorded by physicians in Taiwan NHI outpatient claims data in 2018 had moderate sensitivity and high specificity for both HBV and HCV infection. The PPV was high for HCV ICD-10-CM codes, yet moderate for HBV ICD-10-CM codes.
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Affiliation(s)
- Ming-Jen Sheu
- Division of Gastroenterology and Hepatology, Chi Mei Medical Center, Tainan, Taiwan
- Department of Medicinal Chemistry, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Fu-Weng Liang
- Department of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Sheng-Tun Li
- Department of Industrial and Information Management, College of Management, National Cheng Kung University, Tainan, Taiwan
| | - Chung-Yi Li
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan
- Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan
| | - Tsung-Hsueh Lu
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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Sacco R, Facciorusso A. Expanding treatment strategies for hepatocellular carcinoma patients: postoperative adjuvant transarterial chemoembolization. Hepatobiliary Surg Nutr 2020; 9:59-61. [PMID: 32140479 PMCID: PMC7026796 DOI: 10.21037/hbsn.2019.11.33] [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: 10/02/2019] [Accepted: 11/20/2019] [Indexed: 08/30/2023]
Affiliation(s)
- Rodolfo Sacco
- Gastroenterology Unit, Department of Medical Sciences, University of Foggia, Foggia, Italy
| | - Antonio Facciorusso
- Gastroenterology Unit, Department of Medical Sciences, University of Foggia, Foggia, Italy
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Renal Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Patients with Liver Cirrhosis: A Nationwide Cohort Study. Gastroenterol Res Pract 2019; 2019:1743290. [PMID: 31687012 PMCID: PMC6811787 DOI: 10.1155/2019/1743290] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Accepted: 08/29/2019] [Indexed: 12/18/2022] Open
Abstract
Background The use of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) carries a risk of renal function deterioration in cirrhotic patients with ascites. However, whether the long-term use of ACEis/ARBs is safe in cirrhotic patients without ascites remains unknown. Methods In this nationwide cohort study, we identified 311,361 newly diagnosed cirrhotic patients between January 1997 and December 2013. To avoid indication and immortal time biases, patients receiving regular ACEi/ARB therapy, defined as the ACEi/ARB cohort, were matched to patients receiving regular calcium channel blockers (CCBs), defined as the CCB cohort, at a ratio of 1 : 1 by age, sex, and propensity scores for comorbidities and medications (2,188 patients in each cohort). Cumulative incidence rates and multivariate analyses of end-stage renal disease (ESRD) risk were adjusted for competing mortality. Results The 10-year cumulative incidence rates of ESRD were 2.32% (95% confidence interval [CI]: 1.45–3.20) in the ACEi/ARB cohort and 1.70% (95% CI: 1.03–2.36) in the CCB cohort (P = 0.610). In multivariate analyses, ACEi/ARB use was not associated with a higher risk of ESRD in cirrhotic patients (hazard ratio [HR] = 1.15; 95% CI: 0.69–1.94, P = 0.591). In the sensitivity test, the 10-year cumulative incidence rates of ESRD in cirrhotic patients with ascites were 6.50% (95% CI: 0.54–12.46) and 1.24% (95% CI: 0.00–2.71) in ACEi/ARB and CCB cohorts, respectively (P = 0.090). Conclusions Long-term ACEi/ARB use was not associated with a higher risk of ESRD in cirrhotic patients. However, the risk of ESRD tended to increase in cirrhotic patients with ascites.
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Li X, Xu H, Gao P. Fibrosis Index Based on 4 Factors (FIB-4) Predicts Liver Cirrhosis and Hepatocellular Carcinoma in Chronic Hepatitis C Virus (HCV) Patients. Med Sci Monit 2019; 25:7243-7250. [PMID: 31558693 PMCID: PMC6784625 DOI: 10.12659/msm.918784] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Background Although both hepatic fibrosis progression and hepatitis C virus (HCV) contribute to hepatocellular carcinoma (HCC) development, early detection of HCC remains challenging. Therefore, we evaluated clinical markers of fibrosis in HCV patients to improve early HCC diagnosis. Material/Methods Our retrospective study included 711 chronic HCV patients: 249 HCC patients and 462 non-HCC patients. To investigate the predictive ability of non-invasive scores for diagnosing HCC development, we compared 4 blood indices: fibrosis index based on 4 factors (FIB-4), aspartate aminotransferase-to-platelet count ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), and gamma-glutamyl transpeptidase-to-platelet count ratio (GPR). Results HCC patients had significantly higher scores for all fibrosis indices compared to chronic HCV patients without HCC. Moreover, the diagnostic performance of FIB-4 (area under curve, AUC: 0.961) was superior to that of APRI, AAR, and GPR (AUC: 0.636, 0.746, and 0.661, respectively) for prediction of HCC. FIB-4 also out-performed other indices in the prediction of cirrhotic cases, with an AUC of 0.775 compared to other scores, which ranged from an AUC of 0.597 to 0.671. Conclusions Together, these results suggest that FIB-4 is an appropriate diagnostic indicator of liver cirrhosis and HCC in chronic HCV patients in China.
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Affiliation(s)
- Xu Li
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun, Jilin, China (mainland).,Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, The First Hospital of Jilin University, Changchun, Jilin, China (mainland)
| | - Hongqin Xu
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun, Jilin, China (mainland).,Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, The First Hospital of Jilin University, Changchun, Jilin, China (mainland).,Jilin Province Key Laboratory of Infectious Disease, Laboratory of Molecular Virology, Changchun, Jilin, China (mainland)
| | - Pujun Gao
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun, Jilin, China (mainland).,Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, The First Hospital of Jilin University, Changchun, Jilin, China (mainland)
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15
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Chen YC, Teng W, Hsieh YC, Chen WT, Jeng WJ, Huang CH, Lin CC, Chen YC, Lin SM, Lin CY, Sheen IS. Timely eradication of HCV viremia by PegIFN/RBV is crucial in prevention of post RFA recurrence in CHC-HCC patients. J Formos Med Assoc 2019; 118:1239-1246. [PMID: 30581103 DOI: 10.1016/j.jfma.2018.11.014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Revised: 11/07/2018] [Accepted: 11/28/2018] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Secondary prevention of hepatocellular carcinoma (HCC) among patients with chronic hepatitis C (CHC) who achieve sustained virologic response (SVR) with interferon-based therapy has been proved effective. However, tertiary prevention with PegIFN/RBV therapy of HCC recurrence seems limited effect in CHC-HCC patients post curative therapies. This study aims to investigate the timing and impact of PegIFN/RBV treatment on prevention of HCC recurrence in patients after RFA treatment. METHODS From 2013 to 2016, a total of 137 CHC-HCC patients from a 508 patient based cohort receiving complete RFA treatment in Chang Gung Memorial Hospital, Linkou Medical Center were retrospectively recruited. Pre-RFA patient demographics were analyzed by cox regression analysis for prediction on tumor recurrence. Statistics analysis was performed with SPSS V.20 (IBM, USA). RESULTS The mean age of the 137 patients were 69.6 year-old and 71.5% of patients were cirrhotic. After propensity score matching, one hundred and two patients were enrolled into the analysis. Fifty-one patients (50%) received PegIFN/RBV therapy and twenty-seven patients (52.9%) achieved SVR. Patients who could achieve SVR had lower tumor recurrence rate than non-SVR and untreated groups (29.6% vs. 66.7% vs. 49.0%, P = 0.030). The effect is more prominent in those achieve SVR prior to compared with after RFA despite not reach statistically significant (26.1% vs. 50.0%, P = 0.334). CONCLUSION Timely treatment with SVR achievement has the lowest tumor recurrence rate in CHC-HCC patients. Secondary prevention might be even more important than tertiary prevention in CHC patients, especially regarding prevention of post RFA HCC recurrence.
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Affiliation(s)
- Ying-Chieh Chen
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan.
| | - Wei Teng
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taiwan; College of Medicine, Chang Gung University, Taiwan.
| | - Yi-Chung Hsieh
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan; College of Medicine, Chang Gung University, Taiwan.
| | - Wei-Ting Chen
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan; College of Medicine, Chang Gung University, Taiwan.
| | - Wen-Juei Jeng
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taiwan; College of Medicine, Chang Gung University, Taiwan; School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taiwan.
| | - Chien-Hao Huang
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan; College of Medicine, Chang Gung University, Taiwan.
| | - Chen-Chun Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan; College of Medicine, Chang Gung University, Taiwan.
| | - Yi-Cheng Chen
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan; College of Medicine, Chang Gung University, Taiwan.
| | - Shi-Ming Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan; College of Medicine, Chang Gung University, Taiwan; School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taiwan.
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan; College of Medicine, Chang Gung University, Taiwan.
| | - I-Shyan Sheen
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan; College of Medicine, Chang Gung University, Taiwan.
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Akateh C, Black SM, Conteh L, Miller ED, Noonan A, Elliott E, Pawlik TM, Tsung A, Cloyd JM. Neoadjuvant and adjuvant treatment strategies for hepatocellular carcinoma. World J Gastroenterol 2019; 25:3704-3721. [PMID: 31391767 PMCID: PMC6676544 DOI: 10.3748/wjg.v25.i28.3704] [Citation(s) in RCA: 109] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 06/13/2019] [Accepted: 06/22/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide and a major cause of cancer-related mortality for which liver resection is an important curative-intent treatment option. However, many patients present with advanced disease and with underlying chronic liver disease and/or cirrhosis, limiting the proportion of patients who are surgical candidates. In addition, the development of recurrent or de novo cancers following surgical resection is common. These issues have led investigators to evaluate the benefit of neoadjuvant and adjuvant treatment strategies aimed at improving resectability rates and decreasing recurrence rates. While high-level evidence to guide treatment decision making is lacking, recent advances in locoregional and systemic therapies, including antiviral treatment and immunotherapy, raise the prospect of novel approaches that may improve the outcomes of patients with HCC. In this review, we evaluate the evidence for various neoadjuvant and adjuvant therapies and discuss opportunities for future clinical and translational research.
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Affiliation(s)
- Clifford Akateh
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Sylvester M Black
- Division of Transplant Surgery, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Lanla Conteh
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Eric D Miller
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Anne Noonan
- Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Eric Elliott
- Division of Diagnostic Radiology, Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Allan Tsung
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Jordan M Cloyd
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
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Demerdash HM, Elyamany AS, Arida E. Impact of direct-acting antivirals on leukocytic DNA telomere length in hepatitis C virus-related hepatic cirrhosis. Eur J Gastroenterol Hepatol 2019; 31:494-498. [PMID: 30444746 DOI: 10.1097/meg.0000000000001306] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND Direct-acting antiviral (DAAs) represent advancement in the management of hepatitis C virus (HCV)-related hepatic cirrhosis. A high proportion of patients achieve a sustained virologic response; eradication of HCV is coupled with a decreased risk of hepatocellular carcinoma. Recent evidence suggests that shortening of the DNA telomere may be linked to cellular senescence as well as predisposition to malignant transformation. OBJECTIVE This study aimed to assess pretreatment leukocytic DNA telomere length in HCV-related cirrhosis and post viral eradication using DAAs. PATIENTS AND METHODS This study included 24 patients with HCV-related cirrhosis, Child-Pugh A. Whole-blood samples were obtained from patients before treatment and 12 weeks after the end of treatment, as well as from 24 healthy controls. Terminal restriction fragment, corresponding to telomere length, was measured using a nonradioactive Southern blot technique, detected by chemiluminescence. RESULTS DNA telomere length was significantly shorter before treatment compared with 12 weeks after end of treatment in HCV-related cirrhotic patients. Also, it was significantly shorter in patients before treatment compared with healthy individuals. CONCLUSION Telomere elongation in blood leukocytes can be considered a marker of recovery of inflammation after DAAs-induced HCV eradication. Still, the possibility of activation by cancer initiation cannot be excluded.
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Affiliation(s)
- Hala M Demerdash
- Departments of Clinical Pathology, Alexandria University Hospitals
| | | | - Emad Arida
- Anaesthesia and Intensive Care, Faculty of Medicine, Alexandria University, Alexandria, Egypt
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18
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Tung CH, Lai NS, Li CY, Tsai SJ, Chen YC, Chen YC. Risk of rheumatoid arthritis in patients with hepatitis C virus infection receiving interferon-based therapy: a retrospective cohort study using the Taiwanese national claims database. BMJ Open 2018; 8:e021747. [PMID: 30037875 PMCID: PMC6059328 DOI: 10.1136/bmjopen-2018-021747] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVES To illuminate the association between interferon-based therapy (IBT) and the risk of rheumatoid arthritis (RA) in patients infected with hepatitis C virus (HCV). DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS This retrospective cohort study used Taiwan's Longitudinal Health Insurance Database 2005 that included 18 971 patients with HCV infection between 1 January 1997 and 31 December 2012. We identified 1966 patients with HCV infection who received IBT (treated cohort) and used 1:4 propensity score-matching to select 7864 counterpart controls who did not receive IBT (untreated cohort). OUTCOME MEASURES All study participants were followed until the end of 2012 to calculate the incidence rate and risk of incident RA. RESULTS During the study period, 305 RA events (3.1%) occurred. The incidence rate of RA was significantly lower in the treated cohort than the untreated cohort (4.0 compared with 5.5 per 1000 person-years, p<0.018), and the adjusted HR remained significant at 0.63 (95% CI 0.43 to 0.94, p=0.023) in a Cox proportional hazards regression model. Multivariate stratified analyses revealed that the attenuation in RA risk was greater in men (0.35; 0.15 to 0.81, p=0.014) and men<60 years (0.29; 0.09 to 0.93, p=0.036). CONCLUSIONS This study demonstrates that IBT may reduce the risk of RA and contributes to growing evidence that HCV infection may lead to development of RA.
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Affiliation(s)
- Chien-Hsueh Tung
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Ning-Sheng Lai
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Chung-Yi Li
- Department and Graduate Institute of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan
| | - Shiang-Jiun Tsai
- Department of Medical Research, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Yen-Chun Chen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Yi-Chun Chen
- School of Medicine, Tzu Chi University, Hualien, Taiwan
- Division of Nephrology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
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19
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Wu J, Yin Z, Cao L, Xu X, Yan T, Liu C, Li D. Adjuvant pegylated interferon therapy improves the survival outcomes in patients with hepatitis-related hepatocellular carcinoma after curative treatment: A meta-analysis. Medicine (Baltimore) 2018; 97:e11295. [PMID: 29995763 PMCID: PMC6076097 DOI: 10.1097/md.0000000000011295] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2017] [Accepted: 05/28/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common cancers and the second leading cause of cancer-related deaths in men worldwide. Surgical resection of HCC remains the mainstay treatment procedure. As a result of hepatitis viral infection, the postoperative survival outcome in patients with HCC is not satisfactory. Recently, studies have reported that due to its treatment effect on hepatitis infection, pegylated interferon (Peg-IFN)-based therapy could improve the survival outcome after the treatment of hepatitis-related HCC. However, the postoperative effect of this regimen on the survival outcomes in patients with hepatitis-related HCC remains debatable. The present study conducted a meta-analysis to evaluate the effects of adjuvant Peg-IFN-based therapy on the survival outcomes in patients with hepatitis-related HCC after the curative treatment. METHODS A systematic search was conducted to identify studies on the survival outcomes in patients with hepatitis-related HCC after a curative treatment with adjuvant Peg-IFN. PubMed, EmBase, and Cochrane Library databases were searched until September 20, 2017. The retrieved studies were independently assessed by 2 reviewers, to identify the potentially eligible studies and extract data of interest. STATA software (Version 10.0, STATA Corporation, College Station, Texas) software was used for all statistical analyses. RESULTS The pooled results showed that adjuvant Peg-IFN-based therapy improved the 3- and 5-year recurrence-free survival (RFS) rates of patients with hepatitis-related HCC (3-year RFS, HR = 0.80; 95% CI: 0.64-0.99, P = .04; P = .81 for heterogeneity; 5-year RFS, HR = 0.82; 95% CI: 0.67-0.99, P = .04; P = .84 for heterogeneity). For the 5-year overall survival (OS) outcomes of Peg-IFN therapy for hepatitis-related HCC after the curative treatment, the pooled results showed a significant difference between the 2 groups (HR = 0.67; 95% CI: 0.47-0.97, P = .03; P = .99 for heterogeneity). CONCLUSIONS Adjuvant Peg-IFN-based therapy could improve the RFS and OS outcomes in patients after curative treatment of hepatitis-related HCC, with no severe adverse effects.
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Affiliation(s)
- Jiansong Wu
- Department of Infection Disease, General Hospital of the PLA Rocket Force
| | - Zhiwei Yin
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Disease
| | - Liuxia Cao
- Department of Infection Disease, General Hospital of the PLA Rocket Force
| | - Xiaodan Xu
- Department of Infection Disease, General Hospital of the PLA Rocket Force
| | - Tao Yan
- Department of Hepatobiliary Surgery, General Hospital of the PLA Rocket Force
| | - Changting Liu
- Nanlou Respiratory Diseases Department, Chinese PLA General Hospital, Beijing, China
| | - Diangeng Li
- Nanlou Respiratory Diseases Department, Chinese PLA General Hospital, Beijing, China
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Liu X, Gao Y, Niu J. Hepatitis C Virus - Related Hepatocellular Carcinoma in the Era of Direct - Acting Antiviral Agents. HEPATITIS MONTHLY 2018; 18. [DOI: 10.5812/hepatmon.66007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Murcia Ó, Carnicer F, Gómez-Escolar L, Miralles C, Griñó MP, Barquero Martín C, Pascual S. Direct antiviral agents against hepatitis C virus: Beneficial or harmful? J Hepatol 2018; 68:844-845. [PMID: 29100994 DOI: 10.1016/j.jhep.2017.10.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Accepted: 10/07/2017] [Indexed: 12/04/2022]
Affiliation(s)
- Óscar Murcia
- Department of Hepatology, Hospital General Universitario de Alicante, Spain.
| | - Fernando Carnicer
- Department of Hepatology, Hospital General Universitario de Alicante, Spain
| | | | | | | | | | - Sonia Pascual
- Department of Hepatology, Hospital General Universitario de Alicante, Spain
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Ramadori G, Bosio P, Moriconi F, Malik IA. Case report: 8 years after liver transplantation: de novo hepatocellular carcinoma 8 months after HCV clearance through IFN-free antiviral therapy. BMC Cancer 2018; 18:257. [PMID: 29510685 PMCID: PMC5840818 DOI: 10.1186/s12885-018-4175-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2017] [Accepted: 03/01/2018] [Indexed: 12/14/2022] Open
Abstract
Background After orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC), recurrent HCC mostly develops within 2 years. All cases of de novo HCC described so far occurred later than 2 years after OLT. Prevention of post-transplantation HCC has usually been tried to achieve by curing or controlling recurrent liver disease. This has been rationale for treatment with interferon (IFN)/ribavirin of HCV-recurrence in patients after OLT, transplanted for advanced HCV-induced liver disease and/or HCC. The availability of new and more efficient drugs has improved chances also for previously difficult-to-treat HCV-positive patients. Case presentation A 75 year-old male patient who had undergone OLT for decompensated HCV-cirrhosis in 2009, and bilio-digestive surgery in 2011 under tracrolimus (0.5 mg/day) and prednisone (5 mg/day) immunosuppressive therapy, started to receive antiviral treatment for recurrent HCV-infection of graft with 200 mg/day ribavirin in combination with ledipasvir and sofosbuvir by the end of October 2015. Because of multiple side effects (anemia, asthenia, infections, and reduction of kidney functions - palliated by treatment with erythropoietin), treatment was stopped after 16 weeks. At the third control, a minimal increase in alpha-fetoprotein (AFP) serum level to 10 μg/L was measured 8 months after therapy, whereas both liver sonography and serum transaminases were normal. The patient’s general condition; however, remained poor, and a magnetic resonance imaging (MRI) of abdomen was performed 2 months later. A nodule of 3 cm in diameter with a pseudocapsule was found centrally in the liver. The patient had to be hospitalized for recurrent infections of the lung, overt ascites and peritonitis. Rapid tumor growth (10 cm) was detected during last stay in hospital (April 2017), concomitant with a rise of AFP-serum levels to 91 μg/L. The family decided to take the patient home, and best supportive care was provided by a general practitioner, local nurses and the patient’s dedicated wife until his death. Conclusion Before treating OLT patients with HCV graft reinfection one should not only consider possible advantages of newly effective antiviral-therapies, but also life expectancy and possible side effects (difficult to manage at an outpatient service basis), including severe disadvantages such as the development of HCC.
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Affiliation(s)
- Giuliano Ramadori
- Department of Gastroenterology and Endocrinology, University Medical Center Goettingen, Robert-Koch-Street 40, D-37075, Goettingen, Germany.
| | - Patrizia Bosio
- General Practitioner, National health care system, Palazzago, BG, Italy
| | | | - Ihtzaz A Malik
- Institute of Anatomy and Cell Biology, University Medical Center, Kreuzbering 36, 37075, Goettingen, Germany
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Lee PC, Chen YT, Chao Y, Huo TI, Li CP, Su CW, Lee MH, Hou MC, Lee FY, Lin HC, Huang YH. Validation of the albumin-bilirubin grade-based integrated model as a predictor for sorafenib-failed hepatocellular carcinoma. Liver Int 2018; 38:321-330. [PMID: 28736952 DOI: 10.1111/liv.13527] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Accepted: 07/18/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Sorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC) but is challenging after treatment failure. Appropriate criteria for enrolling patients into second-line trials are still limited. In this study, we aimed to establish more objective criteria based on Albumin-Bilirubin (ALBI) grade to select patients with better post-progression survival (PPS) for second-line treatment. METHODS Consecutive 404 advanced HCC patients receiving sorafenib were retrospectively enrolled. All patients were in Child-Pugh class A and BCLC stage C with either portal vein invasion or extrahepatic metastasis at the beginning of sorafenib treatment. Radiological evaluation based on mRECIST criteria and clinical assessments with compliance were performed on schedule. RESULTS During the median follow-up period of 5.8 months, 310 patients developed progressive disease (PD) and 350 deaths occurred. The PD patients were randomized into derivation and validation cohorts by a 1:1 ratio. The independent predictors of poor PPS in derivation cohort were ALBI grade 3 at PD (hazard ratio [HR]=3.24, P = .002), new extrahepatic lesions (NEH) (HR=1.75, P = .011), and early PD within 4 months (HR=1.88, P = .037). ALBI-PD criteria were proposed by incorporating these three risk factors. In the validation cohort, PPS could be independently predicted by presence of early PD, NEH as well as ALBI grade 3 at PD. Patients within ALBI-PD criteria had significant longer median PPS than those beyond it even in Child-Pugh A (9.7 vs 4.9 months, P = .005) subpopulations. CONCLUSIONS The ALBI-PD criteria can differentiate PPS and stratify the patients with advanced HCC for the second-line trials or salvage therapy.
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Affiliation(s)
- Pei-Chang Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Yi-Tzen Chen
- Department of Nursing, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yee Chao
- Cancer Center, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Teh-Ia Huo
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Chung-Pin Li
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chien-Wei Su
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Mei-Hsuan Lee
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Fa-Yauh Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
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Nirei K, Kanda T, Nakamura H, Matsuoka S, Takayama T, Sugitani M, Moriyama M. Persistent Hepatic Inflammation Plays a Role in Hepatocellular Carcinoma After Sustained Virological Response in Patients with HCV Infection. Int J Med Sci 2018; 15:466-474. [PMID: 29559835 PMCID: PMC5859769 DOI: 10.7150/ijms.23147] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Accepted: 02/02/2018] [Indexed: 02/07/2023] Open
Abstract
Objective: Hepatitis C virus (HCV) infection has long been treated with interferon therapy (IFN). Currently, more than 90% of IFN-treated patients show a sustained virological response (SVR) when also treated with ribavirin and/or a protease inhibitor. Histological inflammation and fibrosis improve in IFN-treated patients, which indicates HCV clearance. IFN also reduces the incidence of hepatocellular carcinoma (HCC). However, a small proportion of patients with SVR develop HCC. To investigate the causes of hepatic carcinogenesis after SVR, we compared the liver histological findings before IFN to those after the development of HCC. Patients and methods: In total, 602 patients infected with type C chronic hepatitis or with liver cirrhosis who received IFN therapy during the period from 1992 through 2015 were included in this study. We assessed 14 of the 287 patients who achieved an SVR. Results: HCC was diagnosed by computed tomography, angiography or liver biopsy. The longest time from the SVR until HCC detection was 16.5 years, and the mean was 7.2±4.6 years. Nine of the 14 patients underwent surgery and one radiofrequency ablation. The histological findings of 10 patients were available for comparison. The comparison of the histological findings before treatment with those after the HCC diagnosis revealed an amelioration of liver fibrosis and other inflammatory changes. All ten patients showed improvements in fibrosis and steatosis. However, we observed that mild inflammatory change persisted from 1.8 years to 16.5 years after the confirmation of SVR in all cases. Conclusion: We suspect that persistent histological inflammation is one of the factors contributing to hepatocarcinogenesis (i.e., HCC development) even after successful treatment.
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Affiliation(s)
- Kazushige Nirei
- Division of Gastroenterology and Hepatology, Department of Internal Medicine
| | - Tatsuo Kanda
- Division of Gastroenterology and Hepatology, Department of Internal Medicine
| | - Hitomi Nakamura
- Division of Gastroenterology and Hepatology, Department of Internal Medicine
| | - Shunichi Matsuoka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine
| | | | | | - Mitsuhiko Moriyama
- Division of Gastroenterology and Hepatology, Department of Internal Medicine
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25
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Teng W, Hsieh YC, Lui KW, Chen WT, Hung CF, Huang CH, Chen YC, Jeng WJ, Lin CC, Lin CY, Lin SM, Sheen IS. Eradication of hepatitis C virus profoundly prolongs survival in hepatocellular carcinoma patients receiving transarterial chemoembolization. J Viral Hepat 2017; 24:1160-1167. [PMID: 28643457 DOI: 10.1111/jvh.12745] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Accepted: 05/15/2017] [Indexed: 12/11/2022]
Abstract
Adjuvant pegylated interferon plus ribavirin treatment (PegIFN/RBV) reduces recurrence and prolongs survival in early stage hepatocellular carcinoma (HCC) patients with chronic hepatitis C (CHC) infection receiving resection or ablation. However, the impact of antiviral therapy in intermediate and advanced stage of CHC-HCC patients is uncertain. This study aimed to investigate the impact PegIFN/RBV treatment on recurrence-free interval and survival in patients with HCC receiving transarterial chemoembolization (TACE). From 2010 to 2013, 274 CHC patients from a 1073 patient-based cohort composed of freshly diagnosed HCC and receiving TACE treatment the Chang Gung Memorial Hospital, Linkou Medical Center were recruited. Propensity score matching (PSM) (age, gender, AST to Platelet Ratio Index (APRI), tumour size, tumour number and Child-Turcotte-Pugh score) with the ratio 1:2 for patients with and without PegIFN/RBV treatment was performed. Statistics were performed with SPSS V.20 (IBM, USA). After matching, 153 patients were analysed and 27 patients (17.6%) achieved sustained virologic response (SVR). The 2-year cumulative overall survival rate and recurrence-free survival rate among patients with SVR, non-SVR, and untreated were 85.2% vs 58.3% vs 69.6% (P=.001) and 73.3% vs 53.8% vs 58.5% (P=.013). By Cox regression analysis, non-SVR, untreated, increase CTP score and nonresponder to TACE were independent factors related to mortality. The SVR achieved by PegIFN/RBV treatment markedly improves survival and reduces tumour recurrence in CHC-HCC patients receiving TACE treatment after complete response.
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Affiliation(s)
- W Teng
- Department of Gastroenterology & Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
- College of Medicine, Chang Gung University, Gueishan, Taiwan
| | - Y-C Hsieh
- Department of Gastroenterology & Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan
- College of Medicine, Chang Gung University, Gueishan, Taiwan
| | - K-W Lui
- Department of Radiology, Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan
- College of Medicine, Chang Gung University, Gueishan, Taiwan
| | - W-T Chen
- Department of Gastroenterology & Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan
- College of Medicine, Chang Gung University, Gueishan, Taiwan
| | - C-F Hung
- Department of Radiology, Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan
- College of Medicine, Chang Gung University, Gueishan, Taiwan
| | - C-H Huang
- Department of Gastroenterology & Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan
- College of Medicine, Chang Gung University, Gueishan, Taiwan
| | - Y-C Chen
- Department of Gastroenterology & Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan
- College of Medicine, Chang Gung University, Gueishan, Taiwan
| | - W-J Jeng
- Department of Gastroenterology & Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
- College of Medicine, Chang Gung University, Gueishan, Taiwan
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Gueishan, Taiwan
| | - C-C Lin
- Department of Gastroenterology & Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan
- College of Medicine, Chang Gung University, Gueishan, Taiwan
| | - C-Y Lin
- Department of Gastroenterology & Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan
- College of Medicine, Chang Gung University, Gueishan, Taiwan
| | - S-M Lin
- Department of Gastroenterology & Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan
- College of Medicine, Chang Gung University, Gueishan, Taiwan
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Gueishan, Taiwan
| | - I-S Sheen
- Department of Gastroenterology & Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan
- College of Medicine, Chang Gung University, Gueishan, Taiwan
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26
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Management consensus guideline for hepatocellular carcinoma: 2016 updated by the Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan. J Formos Med Assoc 2017; 117:381-403. [PMID: 29074347 DOI: 10.1016/j.jfma.2017.09.007] [Citation(s) in RCA: 81] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Revised: 08/16/2017] [Accepted: 09/13/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality in Taiwan. To help clinical physicians to manage patients with HCC, the Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan produced the management consensus guideline for HCC. METHODS The recommendations focus on nine important issues on management of HCC, including surveillance, diagnosis, staging, surgery, local ablation, transarterial chemoembolization/transarterial radioembolization/hepatic arterial infusion chemotherapy, systemic therapy, radiotherapy, and prevention. RESULTS The consensus statements were discussed, debated and got consensus in each expert team. And then the statements were sent to all of the experts for further discussion and refinement. Finally, all of the experts were invited to vote for the statements, including the level of evidence and recommendation. CONCLUSION With the development of the management consensus guideline, HCC patients could benefit from the optimal therapeutic modality.
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27
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Bruno S, Di Marco V, Iavarone M, Roffi L, Boccaccio V, Crosignani A, Cabibbo G, Rossi S, Calvaruso V, Aghemo A, Giacomelli L, Craxì A, Colombo M, Maisonneuve P. Improved survival of patients with hepatocellular carcinoma and compensated hepatitis C virus-related cirrhosis who attained sustained virological response. Liver Int 2017; 37:1526-1534. [PMID: 28418617 DOI: 10.1111/liv.13452] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Accepted: 04/10/2017] [Indexed: 02/13/2023]
Abstract
BACKGROUND Few studies examined the outcome of patients with hepatitis C virus (HCV)-related cirrhosis who developed hepatocellular carcinoma (HCC). The relative weight as determinant of death for cancer vs end-stage liver disease (ESLD) and the benefit of HCV eradication remain undefined. This multicentre, retrospective analysis evaluates overall survival (OS), rate of decompensation and tumour recurrence in compensated HCC patients treated with interferon (IFN) according to HCV status since HCC diagnosis. METHODS Two groups of patients with HCV-related cirrhosis and HCC were followed since HCC diagnosis: (i) compensated cirrhotics with prior sustained virological response (SVR) on IFN-based regimens (N=19); (ii) compensated cirrhotics without SVR (viraemic) (N=156). RESULTS Over a median follow-up of 3.0 years since the onset of HCC, OS was longer for HCC patients with SVR than for viraemic patients (log-rank P=.004). The 5-year OS rate was 65.9% in patients with SVR vs 31.9% in viraemic patients. Similar trends were reported for hepatic decompensation (log-rank P=.01) and tumour recurrence (log-rank P=.01). These findings were confirmed at multivariable and propensity score analysis. At propensity analysis, 0/19 compensated patients with SVR died for ESLD vs 7/19 (37%) viraemic patients (P=.004). HCC mortality was similar in the two groups. CONCLUSIONS Hepatocellular carcinoma patients with prior SVR and compensated cirrhosis at the time of tumour diagnosis have prolonged OS than viraemic patients. Given the lack of cirrhosis progression, no SVR patient ultimately died for ESLD while this condition appears the main cause of death among viraemic patients.
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Affiliation(s)
- Savino Bruno
- Humanitas University and IRCCS Istituto Clinico Humanitas, Rozzano, Italy
| | - Vito Di Marco
- Gastroenterology and Hepatology Unit, Di.Bi.M.I.S., University of Palermo, Palermo, Italy
| | - Massimo Iavarone
- Gastroenterology and Hepatology Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Luigi Roffi
- Department of Medicine, ASST Nord Milano, Milan, Italy
| | - Vincenzo Boccaccio
- Humanitas University and IRCCS Istituto Clinico Humanitas, Rozzano, Italy
| | - Andrea Crosignani
- Department of Internal Medicine, A.O. Santi Paolo e Carlo, Milan, Italy
| | - Giuseppe Cabibbo
- Gastroenterology and Hepatology Unit, Di.Bi.M.I.S., University of Palermo, Palermo, Italy
| | - Sonia Rossi
- Humanitas University and IRCCS Istituto Clinico Humanitas, Rozzano, Italy
| | - Vincenza Calvaruso
- Gastroenterology and Hepatology Unit, Di.Bi.M.I.S., University of Palermo, Palermo, Italy
| | - Alessio Aghemo
- Gastroenterology and Hepatology Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Luca Giacomelli
- Department of Surgery and Integrated Diagnostics, University of Genoa, Genoa, Italy
| | - Antonio Craxì
- Gastroenterology and Hepatology Unit, Di.Bi.M.I.S., University of Palermo, Palermo, Italy
| | - Massimo Colombo
- Gastroenterology and Hepatology Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Patrick Maisonneuve
- Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy
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Huang TS, Lin CL, Lu MJ, Yeh CT, Liang KH, Sun CC, Shyu YC, Chien RN. Diabetes, hepatocellular carcinoma, and mortality in hepatitis C-infected patients: A population-based cohort study. J Gastroenterol Hepatol 2017; 32:1355-1362. [PMID: 27930829 DOI: 10.1111/jgh.13670] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Revised: 10/27/2016] [Accepted: 11/27/2016] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIM The effect of diabetes mellitus (DM) on the development of hepatocellular carcinoma (HCC) and all-cause mortality after HCC development in chronic hepatitis C virus (HCV)-infected patients remains inconclusive. This cohort study aimed to investigate these issues using the Taiwanese National Health Insurance Research Database. METHODS We retrieved and enrolled newly diagnosed DM patients with HCV from the Longitudinal Cohort of Diabetes Patients database. Propensity score matching-including age, sex, alcohol-related liver disease, and baseline liver cirrhosis-was used to identify and enroll HCV patients without DM from the Longitudinal Health Insurance Database (n = 1686). A multi-state model was used to investigate transitions from "start-to-HCC," "start-to-death," and "HCC-to-death." RESULTS The multi-state model showed higher cumulative hazards for "start-to-HCC," "start-to-death," and "HCC-to-death" transitions in the DM (vs non-DM) cohort. The cumulative probability of death with or without HCC after 10 years of follow-up was higher in the DM cohort than in the non-DM cohort. Multivariable transition-specific Cox models demonstrated that DM significantly increased the risk for transition from "start-to-HCC" (adjusted hazard ratio [aHR] 1.36; 95% confidence interval [CI] 1.16-1.59; P < 0.001), "start-to-death" (aHR 2.61; 95% CI: 2.05-3.33; P < 0.001), and "HCC-to-death" (aHR 1.36; 95% CI 1.10-1.68; P = 0.005). The effect of liver cirrhosis on "start-to-HCC" and "start-to-death" transitions decreased over time, particularly within 2 years. CONCLUSIONS Diabetes mellitus increased the risk of HCC development in HCV-infected patients and the risk of all-cause mortality in patients with or without HCC.
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Affiliation(s)
- Ting-Shuo Huang
- Department of General Surgery, Chang Gung Memorial Hospital, Keelung, Taiwan.,Department of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Chih-Lang Lin
- Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan.,Liver Research Unit, Chang Gung Memorial Hospital, Keelung, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Mu-Jie Lu
- Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Chau-Ting Yeh
- College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Liver Research Center, Chang Gung Memorial Hospital, Taipei, Taiwan.,Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan
| | - Kung-Hao Liang
- Liver Research Center, Chang Gung Memorial Hospital, Taipei, Taiwan
| | - Chi-Chin Sun
- Department of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Department of Ophthalmology, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Yu-Chiau Shyu
- Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan.,Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan
| | - Rong-Nan Chien
- Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan.,Liver Research Unit, Chang Gung Memorial Hospital, Keelung, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan
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29
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Beste LA, Green PK, Berry K, Kogut MJ, Allison SK, Ioannou GN. Effectiveness of hepatitis C antiviral treatment in a USA cohort of veteran patients with hepatocellular carcinoma. J Hepatol 2017; 67:32-39. [PMID: 28267622 PMCID: PMC6590903 DOI: 10.1016/j.jhep.2017.02.027] [Citation(s) in RCA: 112] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2016] [Revised: 01/20/2017] [Accepted: 02/18/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS Hepatitis C virus (HCV) treatment for patients with hepatocellular carcinoma (HCC) was uncommon before direct-acting antiviral (DAA) medications. Real-world effectiveness of DAAs for HCV in patients with HCC is unclear. We describe rates of sustained virologic response (SVR) with DAA regimens by HCV genotype in patients with a history of HCC. METHODS We identified patients who initiated antiviral treatment between January 1, 2014 and June 30, 2015 in the national Veterans Affairs health care system. Regimens included sofosobuvir, ledipasvir/sofosbuvir, and paritaprevir/ritonavir/ombitasvir and dasabuvir with or without ribavirin. HCC patients were divided into those who were treated with liver transplantation after HCC diagnosis ("HCC/LT" group) and those treated with other modalities prior to antiviral therapy ("HCC" group). RESULTS Of 17,487 HCV treatment recipients, 624 (3.6%) had prior HCC, including 142 with HCC/LT and 482 with HCC. Overall SVR was 91.1% in non-HCC, 74.4% in HCC, and 94.0% in HCC/LT. Among HCC patients, genotype 1 had the highest SVR overall (79.1% in HCC and 96.4% in HCC/LT), and genotype 3 the lowest (47.0% in HCC and 88.9% in HCC/LT). After adjustment for confounders, the presence of HCC was associated with lower likelihood of SVR overall (AOR 0.38 [95% CI 0.29, 0.48], p<0.001). CONCLUSION HCV can be cured with DAAs in the majority of patients with prior HCC, and in virtually all HCC patients post-liver transplant. Deferral of HCV treatment until the post-transplant setting may be considered among HCC patients listed for transplantation. LAY SUMMARY Over three-quarters of patients with hepatocellular carcinoma who have hepatitis C can achieve viral cure with direct-acting antiviral drugs. Among patients with hepatocellular carcinoma who subsequently received liver transplantation, over 90% of patients can achieve viral cure.
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Affiliation(s)
- Lauren A. Beste
- General Medicine Service, Veterans Affairs Puget Sound Health Care System, United States,Health Services Research and Development, Veterans Affairs Puget Sound Health Care System, United States,Division of General internal Medicine, University of Washington, United States, Corresponding author. Address: Veterans Affairs Puget Sound Health Care System, 1660 S. Columbian Way (S-111-Gastro), Seattle, WA 98108, United States. Tel.: +1 206 277 4511; fax: +1 206 764 2232. , (L.A. Beste).
| | - Pamela K. Green
- Health Services Research and Development, Veterans Affairs Puget Sound Health Care System, United States
| | - Kristin Berry
- Health Services Research and Development, Veterans Affairs Puget Sound Health Care System, United States
| | - Matthew J. Kogut
- Diagnostic Imaging Service, Veterans Affairs Puget Sound Health Care System, United States,Division of interventional Radiology, University of Washington, United States
| | - Stephen K. Allison
- Diagnostic Imaging Service, Veterans Affairs Puget Sound Health Care System, United States,Division of interventional Radiology, University of Washington, United States
| | - George N. Ioannou
- Health Services Research and Development, Veterans Affairs Puget Sound Health Care System, United States,Gastroenterology Service, Veterans Affairs Puget Sound Health Care System, United States,Division of Gastroenterology, University of Washington, United States
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30
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Immunological dynamics associated with rapid virological response during the early phase of type I interferon therapy in patients with chronic hepatitis C. PLoS One 2017; 12:e0179094. [PMID: 28614389 PMCID: PMC5470700 DOI: 10.1371/journal.pone.0179094] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Accepted: 05/23/2017] [Indexed: 02/08/2023] Open
Abstract
Type I interferons (IFNs) play an important role in antiviral immunity as well as immunopathogenesis of diverse chronic viral infections. However, the precise mechanisms regulating the multifaceted effects of type I IFNs on the immune system and pathological inflammation still remain unclear. In order to assess the immunological dynamics associated with rapid viral clearance in chronic hepatitis C patients during the acute phase of type I IFN therapy, we analyzed multiple parameters of virological and immunological responses in a cohort of 59 Korean hepatitis C patients who received pegylated IFN-α and ribavirin (IFN/RBV). Most of the Korean patients had favorable alleles in the IFN-λ loci for responsiveness to IFN/RBV (i.e., C/C in rs12979860, T/T in rs8099917, and TT/TT in rs368234815). Rapid virological response (RVR) was determined mainly by the hepatitis C virus genotype. Among the cytokines analyzed, higher plasma levels of IL-17A and FGF were observed in non-RVR patients infected with viral genotype 1 and IP-10 was consistently elevated in RVR group infected with genotype 2 during the early phase of antiviral therapy. In addition, these three cytokines were correlated each other, suggesting a functional linkage of the cytokines in antiviral responses during IFN/RBV therapy. A low baseline frequencies of regulatory T cells and γδ T cells, but high level of group 2 innate lymphoid cells, in peripheral bloods were also significantly associated with the RVR group, implicating a potential role of the cellular immunity during the early phase of IFN/RBV therapy. Therefore, the immunological programs established by chronic hepatitis C and rapid disruption of the delicate balance by exogenous type I IFN might be associated with the subsequent virological outcomes in chronic hepatitis C patients.
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31
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Adhoute X, Sellier F, Fontaine H, Castellani P, Bourlière M. Carcinome hépatocellulaire et traitements antiviraux contre le VHB et le VHC. ONCOLOGIE 2017. [DOI: 10.1007/s10269-017-2710-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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32
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Li X, Xu H, Gao Y, Pan M, Wang L, Gao P. Diabetes mellitus increases the risk of hepatocellular carcinoma in treatment-naïve chronic hepatitis C patients in China. Medicine (Baltimore) 2017; 96:e6508. [PMID: 28353605 PMCID: PMC5380289 DOI: 10.1097/md.0000000000006508] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
We investigated the link between diabetes mellitus (DM) and hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) risk in treatment-naïve chronic hepatitis C (CHC) patients in China.To examine the association between DM and HCC, we conducted a case-control study of 300 Chinese CHC patients with HCC, compared to an age- and sex-matched control group of 517 CHC patients not diagnosed with HCC.We found that DM was more prevalent in the HCC patient group (18.7%) than in the CHC-only patient group (10.8%). We conducted logistic regression analyses adjusting for demographics features and other HCC risk factors and found that DM increased the risk of HCC development nearly 2-fold [adjusted odds ratio (AOR), 95% confidence interval (95% CI), 1.80 (1.17-2.75)]. Meanwhile, the proportion of HCC patients and CHC-only patients with liver cirrhosis were 79.3% and 46.2%, respectively, yielding an AOR of 4.62 (95% CI, 3.31-6.46). Multivariate analyses comparing the risk of HCV-related HCC development in DM patients with and without liver cirrhosis revealed that the estimated AOR (95% CI) for those with liver cirrhosis was 5.60 (2.25-13.96). However, the HCC risk decreased significantly with a later age of diabetes onset (AOR [95% CI], 0.94 [0.89-0.99]).DM was associated with an increased risk for HCC development in treatment-naïve CHC patients in China. Furthermore, liver cirrhosis and an early DM diagnoses further increased the risks of HCC development in patients diagnosed with both CHC and DM.
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Affiliation(s)
- Xu Li
- Department of Hepatology, The First Hospital of Jilin University, Jilin University
| | - Hongqin Xu
- Department of Hepatology, The First Hospital of Jilin University, Jilin University
- Jilin Province Key Laboratory of Infectious Disease, Laboratory of Molecular Virology
| | - Yang Gao
- Department of Neurology, The First Hospital of Jilin University, Jilin University, Changchun, China
| | - Meng Pan
- Department of Hepatology, The First Hospital of Jilin University, Jilin University
| | - Le Wang
- Department of Hepatology, The First Hospital of Jilin University, Jilin University
| | - Pujun Gao
- Department of Hepatology, The First Hospital of Jilin University, Jilin University
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Facciorusso A, Serviddio G, Muscatiello N. Local ablative treatments for hepatocellular carcinoma: An updated review. World J Gastrointest Pharmacol Ther 2016; 7:477-489. [PMID: 27867681 PMCID: PMC5095567 DOI: 10.4292/wjgpt.v7.i4.477] [Citation(s) in RCA: 98] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2016] [Revised: 07/06/2016] [Accepted: 08/18/2016] [Indexed: 02/06/2023] Open
Abstract
Ablative treatments currently represent the first-line option for the treatment of early stage unresectable hepatocellular carcinoma (HCC). Furthermore, they are effective as bridging/downstaging therapies before orthotopic liver transplantation. Contraindications based on size, number, and location of nodules are quite variable in literature and strictly dependent on local expertise. Among ablative therapies, radiofrequency ablation (RFA) has gained a pivotal role due to its efficacy, with a reported 5-year survival rate of 40%-70%, and safety. Although survival outcomes are similar to percutaneous ethanol injection, the lower local recurrence rate stands for a wider application of RFA in hepato-oncology. Moreover, RFA seems to be even more cost-effective than liver resection for very early HCC (single nodule ≤ 2 cm) and in the presence of two or three nodules ≤ 3 cm. There is increasing evidence that combining RFA to transarterial chemoembolization may increase the therapeutic benefit in larger HCCs without increasing the major complication rate, but more robust prospective data is still needed to validate these pivotal findings. Among other thermal treatments, microwave ablation (MWA) uses high frequency electromagnetic energy to induce tissue death via coagulation necrosis. In comparison to RFA, MWA has several theoretical advantages such as a broader zone of active heating, higher temperatures within the targeted area in a shorter treatment time and the lack of heat-sink effect. The safety concerns raised on the risks of this procedure, due to the broader and less predictable necrosis areas, have been recently overcome. However, whether MWA ability to generate a larger ablation zone will translate into a survival gain remains unknown. Other treatments, such as high-intensity focused ultrasound ablation, laser ablation, and cryoablation, are less investigated but showed promising results in early HCC patients and could be a valuable therapeutic option in the next future.
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Yang JD, Aqel BA, Pungpapong S, Gores GJ, Roberts LR, Leise MD. Direct acting antiviral therapy and tumor recurrence after liver transplantation for hepatitis C-associated hepatocellular carcinoma. J Hepatol 2016; 65:859-860. [PMID: 27392425 DOI: 10.1016/j.jhep.2016.06.023] [Citation(s) in RCA: 111] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2016] [Revised: 06/20/2016] [Accepted: 06/21/2016] [Indexed: 02/08/2023]
Affiliation(s)
- Ju Dong Yang
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, United States
| | - Bashar A Aqel
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, Scottsdale, AZ, United States
| | - Surakit Pungpapong
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, Jacksonville, FL, United States
| | - Gregory J Gores
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, United States
| | - Lewis R Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, United States
| | - Michael D Leise
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, United States.
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35
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Omata M, Kanda T, Wei L, Yu ML, Chuang WL, Ibrahim A, Lesmana CRA, Sollano J, Kumar M, Jindal A, Sharma BC, Hamid SS, Dokmeci AK, Al-Mahtab M, McCaughan GW, Wasim J, Crawford DHG, Kao JH, Yokosuka O, Lau GKK, Sarin SK. APASL consensus statements and recommendations for hepatitis C prevention, epidemiology, and laboratory testing. Hepatol Int 2016; 10:681-701. [PMID: 27229718 PMCID: PMC5003900 DOI: 10.1007/s12072-016-9736-3] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Accepted: 04/20/2016] [Indexed: 02/06/2023]
Abstract
The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on "APASL consensus statements and recommendations for management of hepatitis C" in March 2015 to revise the "APASL consensus statements and management algorithms for hepatitis C virus infection" (Hepatol Int 6:409-435, 2012). The working party consisted of expert hepatologists from the Asian-Pacific region gathered at the Istanbul Congress Center, Istanbul, Turkey on 13 March 2015. New data were presented, discussed, and debated during the course of drafting a revision. Participants of the consensus meeting assessed the quality of the cited studies. The finalized recommendations for hepatitis C prevention, epidemiology, and laboratory testing are presented in this review.
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Affiliation(s)
- Masao Omata
- Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu-shi, Yamanashi, 400-8506, Japan.
- The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
| | - Tatsuo Kanda
- Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Lai Wei
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China
| | - Ming-Lung Yu
- Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Wang-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Alaaeldin Ibrahim
- GI/Liver Division, Department of Internal Medicine, University of Benha, Banha, Egypt
| | | | - Jose Sollano
- University Santo Tomas Hospital, Manila, Philippines
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Saeed S Hamid
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan
| | - A Kadir Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Mamun Al-Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, 1000, Bangladesh
| | - Geofferey W McCaughan
- Royal Prince Alfred Hospital, Centenary Institute, University of Sydney, Sydney, Australia
| | - Jafri Wasim
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan
| | - Darrell H G Crawford
- University of Queensland, School of Medicine, Woolloongabba, QLD, 4102, Australia
| | - Jia-Horng Kao
- National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Osamu Yokosuka
- Graduate School of Medicine, Chiba University, Chiba, Japan
| | - George K K Lau
- The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing, China
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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36
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Lee PC, Yeh CM, Hu YW, Chen CC, Liu CJ, Su CW, Huo TI, Huang YH, Chao Y, Chen TJ, Lin HC, Wu JC. Antiplatelet Therapy is Associated with a Better Prognosis for Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma after Liver Resection. Ann Surg Oncol 2016; 23:874-883. [PMID: 27541812 DOI: 10.1245/s10434-016-5520-9] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Recurrence of hepatocellular carcinoma (HCC) with unsatisfactory survival is common after surgical resection. Antiplatelet therapy with aspirin or clopidogrel was recently shown to prevent hepatic carcinogenesis in a murine model, but its effect in humans had not been clarified. This study aimed to investigate the association between antiplatelet therapy and the outcomes for patients with hepatitis B virus (HBV)-related HCC after liver resection. METHODS By analyzing data from the Taiwan National Health Insurance Research Database, 9461 HBV-related HCC patients who had undergone liver resection between January 1997 and December 2011 were identified. After one-to-four matching by sex, age, and propensity score, 442 patients with antiplatelet therapy and 1768 patients without antiplatelet therapy were enrolled for the analysis. The Kaplan-Meier method and modified Cox proportional hazards models were used for survival and multivariable, stratified analyses. RESULTS Recurrence-free survival and overall survival after resection surgery were significantly better after 5 years in the treated cohort than in the untreated cohort (52.8 vs 47.9 %; p = 0.021 and 80.3 vs 65.4 %; p < 0.001, respectively). Besides, antiplatelet therapy reduced the risk of HCC recurrence (hazard ratio [HR] 0.73; p < 0.001) and overall mortality (HR 0.57; p < 0.001) in the multivariable analysis. However, antiplatelet use significantly increased the risk of upper gastrointestinal bleeding (odds ratio [OR] 1.91; p < 0.001). CONCLUSIONS Use of aspirin or clopidogrel was associated with better recurrence-free survival and overall survival among patients with HBV-related HCC after liver resection. However, these agents should be used with caution due to the adverse effects of upper gastrointestinal bleeding.
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Affiliation(s)
- Pei-Chang Lee
- Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Medicine, Yuanshan Branch, Taipei Veterans General Hospital, Yilan, Taiwan
| | - Chiu-Mei Yeh
- Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yu-Wen Hu
- Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.,Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Public Health, National Yang-Ming University, Taipei, Taiwan
| | - Chun-Chia Chen
- Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chia-Jen Liu
- Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan. .,Institute of Public Health, National Yang-Ming University, Taipei, Taiwan. .,Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
| | - Chien-Wei Su
- Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan. .,Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
| | - Teh-Ia Huo
- Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.,Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Yee Chao
- Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.,Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Tzeng-Ji Chen
- Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.,Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan
| | - Han-Chieh Lin
- Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jaw-Ching Wu
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Translational Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan
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37
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Wirth TC, Manns MP. The impact of the revolution in hepatitis C treatment on hepatocellular carcinoma. Ann Oncol 2016; 27:1467-74. [PMID: 27226385 DOI: 10.1093/annonc/mdw219] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2016] [Accepted: 05/18/2016] [Indexed: 12/13/2022] Open
Abstract
Hepatitis C infection represents a global health problem affecting ∼200 million chronically infected patients worldwide. Owing to the development of a fibrogenic and inflammatory micromilieu in the liver, hepatitis C virus (HCV)-infected patients are at a high risk of developing fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The advent of direct-acting antiviral agents (DAAs), however, has spurred a revolution in the treatment of HCV patients with sustained viral response (SVR) rates exceeding 90% in real-life settings. Recent clinical trials suggest that these novel treatments will not only alter the epidemiology of HCV infection but also the incidence of HCV-induced complications including hepatic decompensation, liver transplantation and hepatocarcinogenesis. Here, we summarize data from clinical trials carried out in HCV patients with compensated and decompensated cirrhosis and analyze the impact of viral clearance on HCC development and treatment. Finally, we review and discuss current and future treatment options of HCV patients with HCC in pre- and post-transplantation settings.
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Affiliation(s)
- T C Wirth
- Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover
| | - M P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover German Center for Infectious Diseases (DZIF), Hannover-Braunschweig, Germany
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38
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Lee TY, Lin JT, Zeng YS, Chen YJ, Wu MS, Wu CY. Association between nucleos(t)ide analog and tumor recurrence in hepatitis B virus-related hepatocellular carcinoma after radiofrequency ablation. Hepatology 2016; 63:1517-27. [PMID: 26426978 DOI: 10.1002/hep.28266] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2015] [Accepted: 09/27/2015] [Indexed: 12/24/2022]
Abstract
UNLABELLED Radiofrequency ablation (RFA) is the best choice for curative treatment of hepatocellular carcinoma (HCC) cases not suitable for surgical intervention, but efforts should be made to reduce the risk of tumor recurrence. We aimed to investigate the association between nucleos(t)ide analog (NA) therapy for hepatitis B virus (HBV) and the risk of HCC recurrence post-RFA. Using the Taiwan National Health Insurance Research Database between July 1, 2004 and December 31, 2012, we screened 48,807 patients with newly diagnosed HBV-related HCC. We identified 850 patients (200 patients who used NAs for more than 90 days and 650 who never used NA post-RFA) who received RFA as a potentially curative treatment for HCC. Patients in the NA-treated cohort were randomly matched 1:2 with patients in the untreated cohort by age, sex, cirrhosis, and the time period between RFA and initiation of NA therapy. Finally, 133 patients were recruited in the NA-treated group and 266 in the untreated group for analysis. Cumulative incidences of and hazard ratios (HRs) for HCC recurrence were analyzed after adjusting for competing mortality. The HCC recurrence rate of the NA-treated group was significantly lower than that of the untreated group (2-year recurrence rate: 41.8%; 95% confidence interval [CI]: 32.9-50.6 vs. 54.3%; 95% CI: 48.0-60.6; modified log-rank test: P < 0.05). In modified Cox's regression analysis, NA therapy was independently associated with a decreased risk of HCC recurrence (HR, 0.69; 95% CI: 0.50-0.95; P < 0.05). Multivariate stratified analyses verified the association of NA therapy and decreased HCC recurrence in almost all patient subgroups. CONCLUSION NA therapy was associated with a decreased risk of HCC recurrence among patients with HBV-related HCC post-RFA.
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Affiliation(s)
- Teng-Yu Lee
- Division of Gastroenterology & Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan.,Department of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Jaw-Town Lin
- School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.,Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan.,Center for Health Policy Research and Development, National Health Research Institutes, Miaoli, Taiwan
| | - Yi-Siou Zeng
- Division of Gastroenterology & Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Yi-Ju Chen
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Department of Dermatology, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Ming-Shiang Wu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Ying Wu
- Division of Gastroenterology & Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,College of Public Health and Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.,Department of Life Sciences, National Chung-Hsing University, Taichung, Taiwan
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39
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Wang CH, Wey KC, Mo LR, Chang KK, Lin RC, Kuo JJ. Current trends and recent advances in diagnosis, therapy, and prevention of hepatocellular carcinoma. Asian Pac J Cancer Prev 2016; 16:3595-604. [PMID: 25987009 DOI: 10.7314/apjcp.2015.16.9.3595] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Hepatocellular carcinoma (HCC) has been one of the most fatal malignant tumors worldwide and its associated morbidity and mortality remain of significant concern. Based on in-depth reviews of serological diagnosis of HCC, in addition to AFP, there are other biomarkers: Lens culinaris agglutinin-reactive AFP (AFP-L3), des- carboxyprothrombin (DCP), tyrosine kinase with Ig and eprdermal growth factor (EGF) homology domains 2 (TIE2)-espressing monocytes (TEMs), glypican-3 (GPC3), Golgi protein 73 (GP73), interleukin-6 (IL-6), and squamous cell carcinoma antigen (SCCA) have been proposed as biomarkers for the early detection of HCC. The diagnosis of HCC is primarily based on noninvasive standard imaging methods, such as ultrasound (US), dynamic multiphasic multidetector-row CT (MDCT) and magnetic resonance imaging (MRI). Some experts advocate gadolinium diethyl-enetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and contrast-enhanced US as the promising imaging madalities of choice. With regard to recent advancements in tissue markers, many cuting-edge technologies using genome-wide DNA microarrays, qRT-PCR, and proteomic and inmunostaining studies have been implemented in an attempt to identify markers for early diagnosis of HCC. Only less than half of HCC patients at initial diagnosis are at an early stage treatable with curative options: local ablation, surgical resection, or liver transplant. Transarterial chemoembolization (TACE) is considered the standard of care with palliation for intermediate stage HCC. Recent innovative procedures using drug-eluting-beads and radioembolization using Yttrium-90 may exhibit beneficial effects in HCC treatment. During the past few years, several molecular targeted agents have been evaluated in clinical trials in advanced HCC. Sorafenib is currently the only approved systemic treatment for HCC. It has been approved for the therapy of asymptomatic HCC patients with well-preserved liver function who are not candidates for potentially curative treatments, such as surgical resection or liver transplantation. In the USA, Europe and particularly Japan, hepatitis C virus (HCV) related HCC accounts for most liver cancer, as compared with Asia-Pacific regions, where hepatitis B virus (HBV) may play a more important role in HCC development. HBV vaccination, while a vaccine is not yet available against HCV, has been recognized as a best primary prevention method for HBV-related HCC, although in patients already infected with HBV or HCV, secondary prevention with antiviral therapy is still a reasonable strategy. In addition to HBV and HCV, attention should be paid to other relevant HCC risk factors, including nonalcoholic fatty liver disease due to obesity and diabetes, heavy alcohol consumption, and prolonged aflatoxin exposure. Interestingly, coffee and vitamin K2 have been proven to provide protective effects against HCC. Regarding tertiary prevention of HCC recurrence after surgical resection, addition of antiviral treatment has proven to be a rational strategy.
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Affiliation(s)
- Chun-Hsiang Wang
- Department of Hepatogastroenterology, Tainan Municipal Hospital, Tainan, Taiwan E-mail :
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40
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Liu PH, Huo TI. Surgery for advanced hepatocellular carcinoma: Time to take action. J Surg Oncol 2016; 112:909. [PMID: 26768514 DOI: 10.1002/jso.24122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Po-Hong Liu
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Teh-Ia Huo
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan
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41
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Wu TJ, Chang SS, Li CW, Hsu YH, Chen TC, Lee WC, Yeh CT, Hung MC. Severe Hepatitis Promotes Hepatocellular Carcinoma Recurrence via NF-κB Pathway-Mediated Epithelial-Mesenchymal Transition after Resection. Clin Cancer Res 2015; 22:1800-12. [PMID: 26655845 DOI: 10.1158/1078-0432.ccr-15-0780] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Accepted: 12/01/2015] [Indexed: 02/06/2023]
Abstract
PURPOSE Surgical resection is considered as a curative treatment modality for hepatocellular carcinoma; however, the incidence of postoperative tumor recurrence is high, leading to worse patient survival. Persistent hepatitis (inflammation) is one of the risk factors of tumor recurrence after surgical resection. The aim of this study is to investigate the underlying mechanisms linking liver inflammation to hepatocellular carcinoma progression. EXPERIMENTAL DESIGN In this study, we used a cytokine array to identify important cytokines whose levels are increased in liver microenvironment with severe hepatitis. We evaluated the morphologic changes, migration and invasion ability, and signal transduction in hepatocellular carcinoma cells with or without inflammatory cytokine in vitro Finally, we analyzed the NF-κB signal pathway in tumor specimens from 232 patients with hepatocellular carcinoma by immunohistochemical staining. RESULTS The proinflammatory cytokine TNFα was increased in the peritumoral microenvironment and contributed to tumor recurrence and metastasis. Specifically, TNFα promoted hepatocellular carcinoma cancer cell migration, invasion, and epithelial-mesenchymal transition (EMT) by upregulating the transcriptional regulator, Snail. We identified Snail as a direct target gene downstream of the TNFα-mediated canonical NF-κB activation. In addition, tumor recurrence-free survival of hepatocellular carcinoma patients correlated negatively with high p65 and Snail expression and positively with high E-cadherin expression. CONCLUSIONS Our results establish a signaling axis that explains how inflammatory tumor microenvironment promotes hepatocellular carcinoma recurrence and metastasis. These findings suggest that controlling liver inflammation and/or targeting NF-κB-mediated Snail expression may be a potential therapeutic strategy to prevent hepatocellular carcinoma recurrence after hepatectomy.
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Affiliation(s)
- Ting-Jung Wu
- Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Division of Liver and Transplantation Surgery, Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University Medical School, Taoyuan, Taiwan
| | - Shih-Shin Chang
- Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas
| | - Chia-Wei Li
- Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Yi-Hsin Hsu
- Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Tse-Ching Chen
- Department of Pathology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Wei-Chen Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University Medical School, Taoyuan, Taiwan
| | - Chau-Ting Yeh
- Liver Research Center, Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Mien-Chie Hung
- Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas. Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan. Department of Biotechnology, Asia University, Taichung, Taiwan.
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42
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Wu CY, Lin JT. The changing epidemiology of Asian digestive cancers: From etiologies and incidences to preventive strategies. Best Pract Res Clin Gastroenterol 2015; 29:843-53. [PMID: 26651247 DOI: 10.1016/j.bpg.2015.09.016] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2015] [Revised: 09/02/2015] [Accepted: 09/17/2015] [Indexed: 02/06/2023]
Abstract
Digestive cancers are a major health burden in Asia. Due to the presence of similar "infection-inflammation-cancer" pathways in the carcinogenesis process, eradicating infective pathogens or attenuating relevant inflammatory signaling pathways may reduce digestive cancer incidences and improve patient outcomes. The aim of this paper is to review the recent evidence regarding the epidemiology of three major digestive cancers in Asia: stomach cancer, liver cancer, and colorectal cancer. We focused on the incidence trends, the major etiologies, and especially the potential preventive strategies.
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Affiliation(s)
- Chun-Ying Wu
- Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan; Faculty of Medicine and Graduate Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Public Health and Graduate Institute of Clinical Medicine, China Medical University, Taichung, Taiwan; National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan; Department of Life Sciences, National Chung-Hsing University, Taichung, Taiwan
| | - Jaw-Town Lin
- School of Medicine, Fu Jen Catholic University, Taipei, Taiwan; Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan; Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan.
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43
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Shakado S, Sakisaka S, Chayama K, Okanoue T, Toyoda J, Izumi N, Matsumoto A, Takehara T, Ido A, Hiasa Y, Yoshioka K, Nomura H, Ueno Y, Seike M, Kumada H. Alpha-fetoprotein and des-gamma-carboxy-prothrombin at twenty-four weeks after interferon-based therapy predict hepatocellular carcinoma development. World J Hepatol 2015; 7:2757-2764. [PMID: 26644819 PMCID: PMC4663395 DOI: 10.4254/wjh.v7.i27.2757] [Citation(s) in RCA: 3] [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: 05/30/2015] [Revised: 08/27/2015] [Accepted: 11/13/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate risk factors for development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus-related liver cirrhosis (LC-C). METHODS To evaluate the relationship between clinical factors including virological response and the development of HCC in patients with LC-C treated with interferon (IFN) and ribavirin, we conducted a multicenter, retrospective study in 14 hospitals in Japan. All patients had compensated LC-C with clinical or histological data available. HCC was diagnosed by the presence of typical hypervascular characteristics on computed tomography and/or magnetic resonance imaging. RESULTS HCC was diagnosis in 50 (21.6%) of 231 LC-C patients during a median observation period of 3.8 years after IFN and ribavirin therapy. Patients who developed HCC were older (P = 0.018) and had higher serum levels of pretreatment alpha-fetoprotein (AFP) (P = 0.038). Multivariate analysis revealed the following independent risk factors for HCC development: history of treatment for HCC [P < 0.001, odds ratio (OR) = 15.27, 95%CI: 4.98-59.51], AFP levels of ≥ 10 ng/mL (P = 0.009, OR = 3.89, 95%CI: 1.38-11.94), and des-γ-carboxy prothrombin (DCP) levels of ≥ 40 mAU/mL at 24 wk after the completion of IFN and ribavirin therapy (P < 0.001, OR = 24.43, 95%CI: 4.11-238.67). CONCLUSION We suggested that the elevation of AFP and DCP levels at 24 wk after the completion of IFN and ribavirin therapy were strongly associated with the incidence of HCC irrespective of virological response among Japanese LC-C patients.
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Affiliation(s)
- Satoshi Shakado
- Satoshi Shakado, Shotaro Sakisaka, Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka City, Fukuoka 814-0180, Japan
| | - Shotaro Sakisaka
- Satoshi Shakado, Shotaro Sakisaka, Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka City, Fukuoka 814-0180, Japan
| | - Kazuaki Chayama
- Satoshi Shakado, Shotaro Sakisaka, Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka City, Fukuoka 814-0180, Japan
| | - Takeshi Okanoue
- Satoshi Shakado, Shotaro Sakisaka, Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka City, Fukuoka 814-0180, Japan
| | - Joji Toyoda
- Satoshi Shakado, Shotaro Sakisaka, Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka City, Fukuoka 814-0180, Japan
| | - Namiki Izumi
- Satoshi Shakado, Shotaro Sakisaka, Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka City, Fukuoka 814-0180, Japan
| | - Akihiro Matsumoto
- Satoshi Shakado, Shotaro Sakisaka, Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka City, Fukuoka 814-0180, Japan
| | - Tetsuo Takehara
- Satoshi Shakado, Shotaro Sakisaka, Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka City, Fukuoka 814-0180, Japan
| | - Akio Ido
- Satoshi Shakado, Shotaro Sakisaka, Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka City, Fukuoka 814-0180, Japan
| | - Yoichi Hiasa
- Satoshi Shakado, Shotaro Sakisaka, Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka City, Fukuoka 814-0180, Japan
| | - Kentaro Yoshioka
- Satoshi Shakado, Shotaro Sakisaka, Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka City, Fukuoka 814-0180, Japan
| | - Hideyuki Nomura
- Satoshi Shakado, Shotaro Sakisaka, Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka City, Fukuoka 814-0180, Japan
| | - Yoshiyuki Ueno
- Satoshi Shakado, Shotaro Sakisaka, Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka City, Fukuoka 814-0180, Japan
| | - Masataka Seike
- Satoshi Shakado, Shotaro Sakisaka, Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka City, Fukuoka 814-0180, Japan
| | - Hiromitsu Kumada
- Satoshi Shakado, Shotaro Sakisaka, Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka City, Fukuoka 814-0180, Japan
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Facciorusso A, Del Prete V, Crucinio N, Muscatiello N, Carr BI, Di Leo A, Barone M. Angiotensin receptor blockers improve survival outcomes after radiofrequency ablation in hepatocarcinoma patients. J Gastroenterol Hepatol 2015; 30:1643-1650. [PMID: 25974743 DOI: 10.1111/jgh.12988] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/18/2015] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIM Inhibition of angiotensin II synthesis seems to decrease hepatocellular carcinoma recurrence after radical therapies; however, data on the adjuvant role of angiotensin II receptor 1 blockers (sartans) are still lacking. The aim of the study was to evaluate whether sartans delay time to recurrence and prolong overall survival in hepatocellular carcinoma patients after radiofrequency ablation. METHODS Data on 153 patients were reviewed. The study population was classified into three groups: 73 (47.8%) patients who received neither angiotensin-converting enzyme inhibitors nor sartans (group 1), 49 (32%) patients treated with angiotensin-converting enzyme inhibitors (group 2), and 31 (20.2%) patients treated with sartans (group 3). Survival outcomes were analysed by means of Kaplan-Meier analysis and compared with log-rank test. RESULTS In the whole study population, 85.6% of patients were in Child-Pugh A class and 89.6% in Barcelona Clinic Liver Cancer A stage. Median maximum tumor diameter was 30 mm (10-40) and alpha fetoprotein was 25 (1.1-2100) UI/mL. No differences in baseline characteristics among the three groups were reported. Median overall survival was 48 months (95% confidence interval: 31-58) in group 1, 72 months (49-89) in group 2, and 84 months (58-92) in group 3 (P = 0.02). Median time to recurrence was 26 (15-42), 44 (33-72), and 69 (44-74) months in the three groups, respectively (P = 0.02). Sartan therapy was a significant predictor of longer overall survival and delayed time to recurrence on multivariate analysis. CONCLUSION Sartans significantly improved overall survival and time to recurrence after radiofrequency ablation in hepatocellular carcinoma patients.
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Affiliation(s)
- Antonio Facciorusso
- Gastroenterology Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Valentina Del Prete
- Gastroenterology Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Nicola Crucinio
- Gastroenterology Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Nicola Muscatiello
- Gastroenterology Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Brian I Carr
- Laboratory of Biochemistry and Tumor Biology, National Institute for Digestive Diseases, IRCCS "Saverio de Bellis", Castellana Grotte, Italy
| | - Alfredo Di Leo
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - Michele Barone
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
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Chen YC, Hwang SJ, Li CY, Wu CP, Lin LC. A Taiwanese Nationwide Cohort Study Shows Interferon-Based Therapy for Chronic Hepatitis C Reduces the Risk of Chronic Kidney Disease. Medicine (Baltimore) 2015; 94:e1334. [PMID: 26266379 PMCID: PMC4616715 DOI: 10.1097/md.0000000000001334] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Hepatitis C virus (HCV) infection is a risk factor for chronic kidney disease (CKD). However, it remains unclear whether interferon-based therapy (IBT) for HCV was associated with reduced risk of CKD.From the Taiwan National Health Insurance Research Database, we identified 919 patients who received 3 months or more of IBT as our treated cohort. This cohort was propensity score-matched 1:4 with 3676 controls who had never received IBT for HCV infection (untreated cohort). Cumulative incidences of and hazard ratios (HRs) for CKD were calculated after adjusting for competing mortality.In the matched HCV cohort, the risk of CKD was significantly lower in the treated cohort (7-year cumulative incidence, 2.6%; 95% confidence interval [CI], 0.7%-6.9%) than in the untreated cohort (4%; 95% CI, 3.5%-5.2%) (P < 0.001), with an adjusted HR of 0.42 (95% CI, 0.20-0.92; P = 0.03). The results also held in the overall HCV cohort. The number needed to treat for 1 fewer CKD at 7 years was 58. The reduced risk of CKD was greatest (0.35; 0.14-0.87; P = 0.024) in HCV-infected patients who received 6 months or more of IBT. Multivariable stratified analysis verified that greater risk reduction of CKD was present in HCV-infected patients with hyperlipidemia, diabetes, hypertension, and those without coronary heart disease.In conclusion, IBT, especially for 6 or more months, is associated with reduced risk of CKD in HCV-infected patients. Hyperlipidemia, diabetes, hypertension, and coronary heart disease can modify this association.
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Affiliation(s)
- Yi-Chun Chen
- From the Division of Nephrology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi (Y-CC, L-CL); School of Medicine, Tzu Chi University, Hualien (Y-CC); Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung (S-JH); Department and Graduate Institute of Public Health, College of Medicine, National Cheng Hung University, Tainan (C-YL); Department of Public Health, College of Public Health, China Medical University, Taichung (C-YL); and Public Health Department, New Taipei City Government, Taipei, Taiwan (C-PW)
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Lee TY, Lin JT, Ho HJ, Wu MS, Wu CY. Evaluation of the Effect of Cumulative Operator Experience on Hepatocellular Carcinoma Recurrence after Primary Treatment with Radiofrequency Ablation. Radiology 2015; 276:294-301. [DOI: 10.1148/radiol.15141864] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Analyzing Taiwan's National Health Insurance Research Database to explicate the allocation of health-care resources. ADVANCES IN DIGESTIVE MEDICINE 2015. [DOI: 10.1016/j.aidm.2015.04.001] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
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Gomaa AI, Waked I. Recent advances in multidisciplinary management of hepatocellular carcinoma. World J Hepatol 2015; 7:673-87. [PMID: 25866604 PMCID: PMC4388995 DOI: 10.4254/wjh.v7.i4.673] [Citation(s) in RCA: 64] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 12/17/2014] [Accepted: 01/15/2015] [Indexed: 02/06/2023] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) is increasing, and it is currently the second leading cause of cancer-related death worldwide. Potentially curative treatment options for HCC include resection, transplantation, and percutaneous ablation, whereas palliative treatments include trans-arterial chemoembolization (TACE), radioembolization, and systemic treatments. Due to the diversity of available treatment options and patients' presentations, a multidisciplinary team should decide clinical management of HCC, according to tumor characteristics and stage of liver disease. Potentially curative treatments are suitable for very-early- and early-stage HCC. However, the vast majority of HCC patients are diagnosed in later stages, where the tumor characteristics or progress of liver disease prevent curative interventions. For patients with intermediate-stage HCC, TACE and radioembolization improve survival and are being evaluated in addition to potentially curative therapies or with systemic targeted therapy. There is currently no effective systemic chemotherapy, immunologic, or hormonal therapy for HCC, and sorafenib is the only approved molecular-targeted treatment for advanced HCC. Other targeted agents are under investigation; trials comparing new agents in combination with sorafenib are ongoing. Combinations of systemic targeted therapies with local treatments are being evaluated for further improvements in HCC patient outcomes. This article provides an updated and comprehensive overview of the current standards and trends in the treatment of HCC.
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Affiliation(s)
- Asmaa I Gomaa
- Asmaa I Gomaa, Imam Waked, Hepatology Department, National Liver Institute, Menoufiya University, Shebeen El-Kom 35111, Egypt
| | - Imam Waked
- Asmaa I Gomaa, Imam Waked, Hepatology Department, National Liver Institute, Menoufiya University, Shebeen El-Kom 35111, Egypt
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Yim HJ, Suh SJ, Um SH. Current management of hepatocellular carcinoma: an Eastern perspective. World J Gastroenterol 2015; 21:3826-42. [PMID: 25852267 PMCID: PMC4385529 DOI: 10.3748/wjg.v21.i13.3826] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2014] [Revised: 12/11/2014] [Accepted: 02/12/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death, especially in Eastern areas. With advancements in diagnosis and treatment modalities for HCC, the survival and prognosis of HCC patients are improving. However, treatment patterns are not uniform between areas despite efforts to promote a common protocol. Although many hepatologists in Asian countries may adopt the principles of the Barcelona Clinic Liver Cancer staging system, they are also independently making an effort to expand the indications of each treatment and to combine therapies for better outcomes. Several expanded criteria for liver transplantation in HCC have been developed in Asian countries. Living donor liver transplantation is much more commonly performed in these countries than deceased donor liver transplantation, and it may be preceded by other treatments such as the down-staging of tumors. Local ablation therapies are often combined with transarterial chemoembolization (TACE) and the outcome is comparable to that of surgical resection. The indications of TACE are expanding, and there are new types of transarterial therapies. Although data on drug-eluting beads, TACE, and radioembolization in Asian countries are still relatively sparse compared with Western countries, these methods are gradually gaining popularity because of better tolerability and the possibility of improved response rates. Hepatic arterial infusion chemotherapy and radiotherapy are not included in Western guidelines, but are currently being used actively in several Asian countries. For more advanced HCCs, appropriate combinations of TACE, radiotherapy, and sorafenib can be considered, and emerging data indicate improved outcomes of combination therapies compared with single therapies. To include these paradigm shifts into newer treatment guidelines, more studies may be needed, but they are certainly in progress.
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Bruix J, Han KH, Gores G, Llovet JM, Mazzaferro V. Liver cancer: Approaching a personalized care. J Hepatol 2015; 62:S144-56. [PMID: 25920083 PMCID: PMC4520430 DOI: 10.1016/j.jhep.2015.02.007] [Citation(s) in RCA: 228] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2014] [Revised: 02/03/2015] [Accepted: 02/04/2015] [Indexed: 12/04/2022]
Abstract
The knowledge and understanding of all aspects of liver cancer [this including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA)] have experienced a major improvement in the last decades. New laboratory technologies have identified several molecular abnormalities that, at the very end, should provide an accurate stratification and optimal treatment of patients diagnosed with liver cancer. The seminal discovery of the TP53 hotspot mutation [1 ,2 ] was an initial landmark step for the future classification and treatment decision using conventional clinical criteria blended with molecular data. At the same time, the development of ultrasound, computed tomography (CT) and magnetic resonance (MR) has been instrumental for earlier diagnosis, accurate staging and treatment advances. Several treatment options with proven survival benefit if properly applied are now available. Major highlights include: i) acceptance of liver transplantation for HCC if within the Milan criteria [3 ], ii) recognition of ablation as a potentially curative option [4 ,5 ], iii) proof of benefit of chemoembolization (TACE), [6 ] and iv) incorporation of sorafenib as an effective systemic therapy [7 ]. These options are part of the widely endorsed BCLC staging and treatment model (Fig. 1 ) [8 ,9 ]. This is clinically useful and it will certainly keep evolving to accommodate new scientific evidence. This review summarises the data which are the basis for the current recommendations for clinical practice, while simultaneously exposes the areas where more research is needed to fulfil the still unmet needs (Table 1 ).
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Affiliation(s)
- Jordi Bruix
- Barcelona Clinic Liver Cancer Group (BCLC), Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Universitat de Barcelona, Catalonia, Spain.
| | - Kwang-Hyub Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Gregory Gores
- Mayo Clinic, Mayo College of Medicine, Rochester, MN, USA
| | - Josep Maria Llovet
- Barcelona Clinic Liver Cancer Group (BCLC), Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Universitat de Barcelona, Catalonia, Spain; Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, USA; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain
| | - Vincenzo Mazzaferro
- Gastrointestinal Surgery and Liver Transplantation, Istituto Nazionale Tumori IRCCS (National Cancer Institute), Milan 20133, Italy
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