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Huang GQ, Xie YY, Zhu PW, Wang XD, Lin Z, Wang Y, Ye JP, Wang YM, Chen YX, Jin XZ, Van Poucke S, Chen YP, Zheng MH. Stratified alpha-fetoprotein pattern accurately predicts mortality in patients with acute-on-chronic hepatitis B liver failure. Expert Rev Gastroenterol Hepatol 2018; 12:295-302. [PMID: 29300103 DOI: 10.1080/17474124.2018.1424540] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Alpha-fetoprotein (AFP) has been shown to predict the prognosis of liver disease in several studies. This study aimed to evaluate the prognostic value of stratified AFP in patients with acute-on-chronic hepatitis B liver failure (ACHBLF). METHODS A total of 192 patients were included and AFP were categorized into quartiles. The prognostic value was determined for overall survival (OS) and assessed by Kaplan-Meier analysis. Univariate and multivariate Cox proportional hazard regression analyses studied the association of all independent parameters with disease prognosis. RESULTS The optimal cut-off points of AFP were: (Q1) 252.3-4800.0 ng/ml, (Q2) 76.0-252.2 ng/ml, (Q3) 18.6-75.9 ng/ml, and (Q4) 0.7-18.5 ng/ml. Based on the Kaplan-Meier analysis of the OS, each AFP quartile revealed a progressively worse OS and apparent separation (log-rank P = 0.006). The second-highest quartiles of AFP (Q2) always demonstrated an extremely favorable short-term survival. Combining the lowest AFP quartiles with a serum sodium < 131mmol/L or an INR ≥ 3.3 showed a poor outcome (90-days survival of 25.0% and 11.9% respectively). CONCLUSIONS Stratified AFP could strengthen the predictive power for short-term survival of patients with ACHBLF. Combining AFP quartiles with low serum sodium and high INR may better predict poor outcome in ACHBLF patients.
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Affiliation(s)
- Gui-Qian Huang
- a Department of Hepatology, Liver Research Center , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
- b Department of Neurology , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
| | - Yao-Yao Xie
- c Department of Clinical Laboratory , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
| | - Pei-Wu Zhu
- c Department of Clinical Laboratory , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
| | - Xiao-Dong Wang
- a Department of Hepatology, Liver Research Center , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
- d Institute of Hepatology , Wenzhou Medical University , Wenzhou , China
| | - Zhuo Lin
- a Department of Hepatology, Liver Research Center , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
- d Institute of Hepatology , Wenzhou Medical University , Wenzhou , China
| | - Yan Wang
- a Department of Hepatology, Liver Research Center , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
| | - Jiang-Pin Ye
- a Department of Hepatology, Liver Research Center , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
| | - Yu-Min Wang
- c Department of Clinical Laboratory , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
| | - Ying-Xiao Chen
- a Department of Hepatology, Liver Research Center , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
| | - Xiao-Zhi Jin
- a Department of Hepatology, Liver Research Center , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
| | - Sven Van Poucke
- e Department of Anesthesiology, Intensive Care, Emergency Medicine and Pain Therapy , Ziekenhuis Oost-Limburg , Genk , Belgium
| | - Yong-Ping Chen
- a Department of Hepatology, Liver Research Center , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
- d Institute of Hepatology , Wenzhou Medical University , Wenzhou , China
| | - Ming-Hua Zheng
- a Department of Hepatology, Liver Research Center , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
- d Institute of Hepatology , Wenzhou Medical University , Wenzhou , China
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Zheng J, Zhao M, Li J, Lou G, Yuan Y, Bu S, Xi Y. Obesity-associated digestive cancers: A review of mechanisms and interventions. Tumour Biol 2017; 39:1010428317695020. [PMID: 28351315 DOI: 10.1177/1010428317695020] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
The prevalence of obesity has steadily increased over the past few decades. Previous studies suggest that obesity is an oncogenic factor and that over 20% of all cancers are obesity-related. Among such cancers, digestive system malignancies (including esophageal adenocarcinomas, colorectal cancers, and cancers of the gastric cardia, liver, and pancreas) are reported most frequently. While the 5-year survival rates of cancers of the breast and prostate are 90%, that rate is only 45% for digestive cancers. In this review, the mechanisms of obesity-associated digestive cancers are discussed, with an emphasis on obesity-related gene mutations, insulin and insulin-like growth factor signaling pathways, chronic inflammation, and altered adipokine levels. Evidence that these factors often function interdependently rather than independently in carcinogenesis is presented. Recommended interventions that may reduce the burden of obesity-associated digestive cancers, such as participation in physical activity, diet modulation, and calorie restriction, are also described.
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Affiliation(s)
- Jiachen Zheng
- Diabetes Center, Zhejiang Provincial Key Laboratory of Pathophysiology, Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, Ningbo, China
| | - Ming Zhao
- Diabetes Center, Zhejiang Provincial Key Laboratory of Pathophysiology, Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, Ningbo, China
| | - Jiahui Li
- Diabetes Center, Zhejiang Provincial Key Laboratory of Pathophysiology, Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, Ningbo, China
| | - Guoying Lou
- Diabetes Center, Zhejiang Provincial Key Laboratory of Pathophysiology, Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, Ningbo, China
| | - Yanyan Yuan
- Diabetes Center, Zhejiang Provincial Key Laboratory of Pathophysiology, Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, Ningbo, China
| | - Shizhong Bu
- Diabetes Center, Zhejiang Provincial Key Laboratory of Pathophysiology, Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, Ningbo, China
| | - Yang Xi
- Diabetes Center, Zhejiang Provincial Key Laboratory of Pathophysiology, Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, Ningbo, China
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Sanabria JR, Kombu RS, Zhang GF, Sandlers Y, Ai J, Ibarra RA, Abbas R, Goyal K, Brunengraber H. Glutathione species and metabolomic prints in subjects with liver disease as biological markers for the detection of hepatocellular carcinoma. HPB (Oxford) 2016; 18:979-990. [PMID: 28340971 PMCID: PMC5144552 DOI: 10.1016/j.hpb.2016.09.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Revised: 09/04/2016] [Accepted: 09/14/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND The incidence of liver disease is increasing in USA. Animal models had shown glutathione species in plasma reflects liver glutathione state and it could be a surrogate for the detection of hepatocellular carcinoma (HCC). METHODS The present study aimed to translate methods to the human and to explore the role of glutathione/metabolic prints in the progression of liver dysfunction and in the detection of HCC. Treated plasma from healthy subjects (n = 20), patients with liver disease (ESLD, n = 99) and patients after transplantation (LTx, n = 7) were analyzed by GC- or LC/MS. Glutathione labeling profile was measured by isotopomer analyzes of 2H2O enriched plasma. Principal Component Analyzes (PCA) were used to determined metabolic prints. RESULTS There was a significant difference in glutathione/metabolic profiles from patients with ESLD vs healthy subjects and patients after LTx. Similar significant differences were noted on patients with ESLD when stratified by the MELD score. PCA analyses showed myristic acid, citric acid, succinic acid, l-methionine, d-threitol, fumaric acid, pipecolic acid, isoleucine, hydroxy-butyrate and glycolic, steraric and hexanoic acids were discriminative metabolites for ESLD-HCC+ vs ESLD-HCC- subject status. CONCLUSIONS Glutathione species and metabolic prints defined liver disease severity and may serve as surrogate for the detection of HCC in patients with established cirrhosis.
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Affiliation(s)
- Juan R. Sanabria
- Department of Surgery, Case Western Reserve University School of Medicine, Cleveland, OH, USA,Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH, USA,Department of Preventive Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA,Department of Surgery and Research, Cancer Treatment Centers of America, Chicago, IL, USA,Department of Biostatistics, Cancer Treatment Centers of America, Chicago, IL, USA,Correspondence Juan R. Sanabria, Department of Surgery at Marshall University or Department of Proteomics and Metabolmics Core Facilities at Case Western Reserve University, Cleveland, OH, USA.Department of Surgery at Marshall University or Department of Proteomics and Metabolmics Core Facilities at Case Western Reserve UniversityClevelandOHUSA
| | - Rajan S. Kombu
- Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Guo-Fang Zhang
- Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Yana Sandlers
- Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Jizhou Ai
- Department of Surgery and Research, Cancer Treatment Centers of America, Chicago, IL, USA,Department of Biostatistics, Cancer Treatment Centers of America, Chicago, IL, USA
| | - Rafael A. Ibarra
- Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Rime Abbas
- Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Kush Goyal
- Department of Surgery, Case Western Reserve University School of Medicine, Cleveland, OH, USA,Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Henri Brunengraber
- Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH, USA,Department of Metabolomics and Proteomics Core Facilities, Case Western Reserve University School of Medicine, Cleveland, OH, USA
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Soriano A, Varona A, Gianchandani R, Moneva ME, Arranz J, Gonzalez A, Barrera M. Selection of patients with hepatocellular carcinoma for liver transplantation: Past and future. World J Hepatol 2016; 8:58-68. [PMID: 26783421 PMCID: PMC4705453 DOI: 10.4254/wjh.v8.i1.58] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 11/18/2015] [Accepted: 12/11/2015] [Indexed: 02/06/2023] Open
Abstract
The aim of liver transplantation (LT) for hepatocellular carcinoma (HCC) is to ensure a rate of disease-free survival similar to that of patients transplanted due to benign disease. Therefore, we are forced to adopt strict criteria when selecting candidates for LT and prioritizing patients on the waiting list (WL), to have clarified indications for bridging therapy for groups at risk for progression or recurrence, and to establish certain limits for downstaging therapies. Although the Milan criteria (MC) remain the standard and most employed criteria for indication of HCC patients for LT by far, in the coming years, criteria will be consolidated that take into account not only data regarding the size/volume and number of tumors but also their biology. This criteria will mainly include the alpha fetoprotein (AFP) values and, in view of their wide variability, any of the published logarithmic models for the selection of candidates for LT. Bridging therapy is necessary for HCC patients on the WL who meet the MC and have the possibility of experiencing a delay for LT greater than 6 mo or any of the known risk factors for recurrence. It is difficult to define single AFP values that would indicate bridging therapy (200, 300 or 400 ng/mL); therefore, it is preferable to rely on the criteria of a French AFP model score > 2. Other single indications for bridging therapy include a tumor diameter greater than 3 cm, more than one tumor, and having an AFP slope greater than 15 ng/mL per month or > 50 ng/mL for three months during strict monitoring while on the WL. When considering the inclusion of patients on the WL who do not meet the MC, it is mandatory to determine their eligibility for downstaging therapy prior to inclusion. The upper limit for this therapy could be one lesion up to 8 cm, 2-3 lesions with a total tumor diameter up to 8 cm, or a total tumor volume of 115 cm3. Lastly, liver allocation and the prioritization of patients with HCC on the WL should take into account the recently described HCC model for end-stage liver disease, which considers hepatic function, HCC size and the number and the log of AFP values. This formula has been calibrated with the survival data of non-HCC patients and produces a dynamic and more accurate assessment model.
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Waller LP, Deshpande V, Pyrsopoulos N. Hepatocellular carcinoma: A comprehensive review. World J Hepatol 2015; 7:2648-2663. [PMID: 26609342 PMCID: PMC4651909 DOI: 10.4254/wjh.v7.i26.2648] [Citation(s) in RCA: 137] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Revised: 05/19/2015] [Accepted: 10/14/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is rapidly becoming one of the most prevalent cancers worldwide. With a rising rate, it is a prominent source of mortality. Patients with advanced fibrosis, predominantly cirrhosis and hepatitis B are predisposed to developing HCC. Individuals with chronic hepatitis B and C infections are most commonly afflicted. Different therapeutic options, including liver resection, transplantation, systemic and local therapy, must be tailored to each patient. Liver transplantation offers leading results to achieve a cure. The Milan criteria is acknowledged as the model to classify the individuals that meet requirements to undergo transplantation. Mean survival remains suboptimal because of long waiting times and limited donor organ resources. Recent debates involve expansion of these criteria to create options for patients with HCC to increase overall survival.
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Affiliation(s)
- Lisa P Waller
- Lisa P Waller, Vrushak Deshpande, Nikolaos Pyrsopoulos, Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Vrushak Deshpande
- Lisa P Waller, Vrushak Deshpande, Nikolaos Pyrsopoulos, Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Nikolaos Pyrsopoulos
- Lisa P Waller, Vrushak Deshpande, Nikolaos Pyrsopoulos, Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
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