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Yao Y, Zhang M, Liu D, Liu X, Li Q, Wang X. Changes in systemic immune-inflammation index (SII) predict the prognosis of patients with hepatitis B-related hepatocellular carcinoma treated with lenvatinib plus PD-1 inhibitors. Clin Transl Oncol 2025; 27:1155-1165. [PMID: 39153177 DOI: 10.1007/s12094-024-03596-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 07/03/2024] [Indexed: 08/19/2024]
Abstract
PURPOSE This study aimed to evaluate the prognostic significance of changes in inflammatory markers in patients with Hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) treated with first-line lenvatinib plus a programmed cell death protein 1 (PD-1) inhibitor. METHODS This study retrospectively included 117 HBV-HCC patients treated with first-line lenvatinib in combination with a PD-1 inhibitor. Independent factors affecting progression-free survival (PFS) and overall survival (OS) were explored based on baseline indicators and inflammatory markers changes after one treatment cycle. RESULTS Multivariate analysis revealed that an alpha-fetoprotein (AFP) level ⩾ 400 ng/mL [hazard ratio (HR), 1.69; 95% confidence interval (CI), 1.11-2.58; P = 0.01] was identified as an independent risk factor, platelet-to-neutrophil ratio (PNR) ⩽ 65.43 (HR 0.50; 95% CI 0.30-0.84; P < 0.01 ) and SII ⩽ 539.47 (HR 0.54; 95% CI 0.30-0.96; P = 0.03) were identified as independent protective factors for PFS. Additionally, multivariate analysis demonstrated that AFP ⩾ 400 ng/mL, HBV-HCC patients with diabetes mellitus (DM), and SII > 303.66 were independent risk factors of OS. The patients whose SII had increased after one cycle of treatment showed a poorer PFS (HR 1.61; 95 %CI 1.10-2.37; P = 0.015) and OS (HR 1.76; 95 % CI 1.15-2.70; P = 0.009) than patients whose SII had decreased. The objective response rate (ORR) was higher in the SII-decreased patients (47.5% vs 32.5%, P = 0.11). Mann-Whitney test found a significant difference in therapeutic response between the SII-increased patients and the SII-decreased patients (P = 0.04). CONCLUSION SII can be associated with outcomes in patients with HBV-HCC treated with first-line lenvatinib plus PD-1 inhibitors.
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Affiliation(s)
- Yang Yao
- Department of Integrated Traditional Chinese and Western Medicine, Beijing Youan Hospital, Capital Medical University, No. 8 Xi Tou Tiao, You An Men Wai, Feng Tai District, Beijing, 100069, China
| | - Minyue Zhang
- Department of Integrated Traditional Chinese and Western Medicine, Beijing Youan Hospital, Capital Medical University, No. 8 Xi Tou Tiao, You An Men Wai, Feng Tai District, Beijing, 100069, China
| | - Di Liu
- Department of Integrated Traditional Chinese and Western Medicine, Beijing Youan Hospital, Capital Medical University, No. 8 Xi Tou Tiao, You An Men Wai, Feng Tai District, Beijing, 100069, China
| | - Xiaoni Liu
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, No. 8 Xi Tou Tiao, You An Men Wai, Feng Tai District, Beijing, 100069, China
| | - Quanwei Li
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, No. 8 Xi Tou Tiao, You An Men Wai, Feng Tai District, Beijing, 100069, China
| | - Xiaojun Wang
- Department of Integrated Traditional Chinese and Western Medicine, Beijing Youan Hospital, Capital Medical University, No. 8 Xi Tou Tiao, You An Men Wai, Feng Tai District, Beijing, 100069, China.
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Wu L, Chen L, Zhang L, Liu Y, Ouyang D, Wu W, Lei Y, Han P, Zhao H, Zheng C. A Machine Learning Model for Predicting Prognosis in HCC Patients With Diabetes After TACE. J Hepatocell Carcinoma 2025; 12:77-91. [PMID: 39867262 PMCID: PMC11762020 DOI: 10.2147/jhc.s496481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Accepted: 01/10/2025] [Indexed: 01/28/2025] Open
Abstract
Purpose Type II diabetes mellitus (T2DM) has been found to increase the mortality of patients with hepatocellular carcinoma (HCC). Therefore, this study aimed to establish and validate a machine learning-based explainable prediction model of prognosis in patients with HCC and T2DM undergoing transarterial chemoembolization (TACE). Patients and Methods The prediction model was developed using data from the derivation cohort comprising patients from three medical centers, followed by external validation utilizing patient data extracted from another center. Further, five predictive models were employed to establish prognosis models for 1-, 2-, and 3-year survival, respectively. Prediction performance was assessed by the receiver operating characteristic (ROC), calibration, and decision curve analysis curves. Lastly, the SHapley Additive exPlanations (SHAP) method was used to interpret the final ML model. Results A total of 636 patients were included. Thirteen variables were selected for the model development. The final random survival forest (RSF) model exhibited excellent performance in the internal validation cohort, with areas under the ROC curve (AUCs) of 0.824, 0.853, and 0.810 in the 1-, 2-, and 3-year survival groups, respectively. This model also demonstrated remarkable discrimination in the external validation cohort, achieving AUCs of 0.862, 0.815, and 0.798 in the 1-, 2-, and 3-year survival groups, respectively. SHAP summary plots were also created to interpret the RSF model. Conclusion An RSF model with good predictive performance was developed by incorporating simple parameters. This prognostic prediction model may assist physicians in early clinical intervention and improve prognosis outcomes in patients with HCC and comorbid T2DM after TACE.
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Affiliation(s)
- Linxia Wu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430022, People’s Republic of China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430022, People’s Republic of China
- Hubei Provincial Clinical Research Center for Precision Radiology & Interventional Medicine, Wuhan, Hubei Province, 430022, People’s Republic of China
| | - Lei Chen
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430022, People’s Republic of China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430022, People’s Republic of China
- Hubei Provincial Clinical Research Center for Precision Radiology & Interventional Medicine, Wuhan, Hubei Province, 430022, People’s Republic of China
| | - Lijie Zhang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430022, People’s Republic of China
- Department of Interventional Radiology, The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, 100039, People’s Republic of China
| | - Yiming Liu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430022, People’s Republic of China
- Department of Interventional Radiology, Auto Valley Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430056, People’s Republic of China
| | - Die Ouyang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430022, People’s Republic of China
| | - Wenlong Wu
- Department of Interventional Radiology, Auto Valley Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430056, People’s Republic of China
- Department of Interventional Radiology, Jinyinhu Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430048, People’s Republic of China
| | - Yu Lei
- Department of Interventional Radiology, Auto Valley Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430056, People’s Republic of China
- Department of Interventional Radiology, Jinyinhu Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430048, People’s Republic of China
| | - Ping Han
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430022, People’s Republic of China
| | - Huangxuan Zhao
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430022, People’s Republic of China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430022, People’s Republic of China
- Hubei Provincial Clinical Research Center for Precision Radiology & Interventional Medicine, Wuhan, Hubei Province, 430022, People’s Republic of China
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430022, People’s Republic of China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430022, People’s Republic of China
- Hubei Provincial Clinical Research Center for Precision Radiology & Interventional Medicine, Wuhan, Hubei Province, 430022, People’s Republic of China
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Chen L, Wu L, Zhang L, Sun B, Wu W, Lei Y, Zhu L, Sun T, Liang B, Zhao H, Zheng C. Effect of metformin on hepatocellular carcinoma patients with type II diabetes receiving transarterial chemoembolization: a multicenter retrospective cohort study. Int J Surg 2025; 111:828-838. [PMID: 38935094 PMCID: PMC11745749 DOI: 10.1097/js9.0000000000001872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 06/17/2024] [Indexed: 06/28/2024]
Abstract
BACKGROUND Diabetes is prevalent among patients with hepatocellular carcinoma (HCC) and is associated with a poor prognosis. Although the hypoglycemic drug metformin has shown antitumor effects, its potential positive effect on patients with HCC and diabetes undergoing transarterial chemoembolization (TACE) remains unclear. Therefore, this study aimed to investigate the efficacy and safety of metformin in patients with HCC and type II diabetes who are receiving TACE. MATERIALS AND METHODS This retrospective study involved 372 consecutive patients with HCC and type II diabetes across three medical centers between January 2014 and June 2021. All patients underwent TACE. Propensity score matching (PSM) was used to reduce selection bias. Cox proportional hazards regression was employed to compare all-cause death between the metformin and nonmetformin groups while competing risk regression was performed to assess cancer-specific death. RESULTS Among 372 patients included in the study, 208 patients (177 male patients and 31 female patients) with a mean age of 59.6 (10.3) years received metformin, and 164 patients (139 male patients and 25 female patients) with a mean age of 60.3 (10.0) years did not. Before PSM, patients with metformin had significantly longer median overall survival (mOS) and median progression-free survival (mPFS) than those without metformin (mOS: 34 months, 95% CI: 25.6-42.4 vs. 20 months, 95% CI: 15.3-24.7; P <0.001; mPFS: 11 months, 95% CI: 9.3-12.7 vs. 8 months, 95% CI: 5.9-10.1; P <0.001). Similar results were observed after PSM. Multivariate regression analysis indicated that metformin was associated with a reduced risk of all-cause mortality (HR: 0.589, 95% CI: 0.454-0.763; P <0.001) and tumor progression (HR: 0.667, 95% CI: 0.526-0.845; P =0.001) before PSM. After excluding deaths related to other factors, metformin continued to demonstrate a reduction in cancer-specific mortality risk among the patients. Subgroup analysis further revealed that patients using metformin had lower all-cause mortality risk and tumor progression risk than those without metformin in most subgroups. Adverse event evaluation suggested that metformin could lead to elevated nausea incidence. CONCLUSION Metformin may confer survival benefits to patients with HCC and type II diabetes undergoing TACE. Metformin may simultaneously address multiple aspects of treatment in these patients.
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Affiliation(s)
- Lei Chen
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
| | - Linxia Wu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
| | - Lijie Zhang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Department of Interventional Radiology, The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, People’s Republic of China
| | - Bo Sun
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
| | - Wenlong Wu
- Department of Interventional Radiology, Chegu Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Yu Lei
- Department of Interventional Radiology, Chegu Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Licheng Zhu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
| | - Tao Sun
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
| | - Bin Liang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Department of Interventional Radiology, Chegu Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Huangxuan Zhao
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
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Shiomi A, Miyake T, Furukawa S, Matsuura B, Yoshida O, Watanabe T, Kanamoto A, Miyazaki M, Nakaguchi H, Tokumoto Y, Hirooka M, Abe M, Hiasa Y. Combined effect of histological findings and diabetes mellitus on liver-related events in patients with metabolic dysfunction-associated steatotic liver disease. Hepatol Res 2024; 54:1016-1026. [PMID: 38656764 DOI: 10.1111/hepr.14049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 04/07/2024] [Accepted: 04/09/2024] [Indexed: 04/26/2024]
Abstract
AIM Advanced fibrosis has a strong influence on the occurrence of liver-related events in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), while diabetes mellitus (DM), which is often complicated by MASLD, is associated with the progression of MASLD. We stratified patients with MASLD according to the severity of liver pathological findings and the presence of DM, aiming to examine whether these indices could be used to accurately assess the risk of developing liver-related events. METHODS A total of 282 patients with liver biopsy-proven MASLD were included. Liver-related events were defined as the occurrence of hepatocellular carcinoma (HCC) and complications of liver cirrhosis, such as ascites, hepatic encephalopathy, Child-Pugh class B and C, as well as treatment-eligible esophageal and gastric varices. RESULTS Multivariate analysis adjusted for age, sex, body mass index, alanine aminotransferase, creatinine, hemoglobin A1c, smoking habits, dyslipidemia, hypertension, nonalcoholic fatty liver disease activity score (NAS), or fibrosis stage showed that advanced fibrosis with or without DM was a risk factor for liver-related events. The combined effect of DM and advanced fibrosis increased the risk of HCC onset. However, DM alone or in combination with NAS did not affect the development of liver-related events, including the occurrence of HCC and complications of liver cirrhosis. CONCLUSIONS While the assessment of fibrosis in patients with MASLD is important for evaluating the risk of developing liver-related events, combining the assessment of DM may be possible to stratify groups at higher risk of developing HCC.
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Affiliation(s)
- Akihito Shiomi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Teruki Miyake
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | | | - Bunzo Matsuura
- Department of Lifestyle-Related Medicine and Endocrinology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Osamu Yoshida
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Takao Watanabe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Ayumi Kanamoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Masumi Miyazaki
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Hironobu Nakaguchi
- Department of Lifestyle-Related Medicine and Endocrinology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Yoshio Tokumoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Masanori Abe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
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Yiu DCY, Lin H, Wong VWS, Wong GLH, Liu K, Yip TCF. Dipeptidyl peptidase-4 inhibitors are associated with improved survival of patients with diabetes mellitus and hepatocellular carcinoma receiving immunotherapy: Letter to the editor on "Statin and aspirin for chemoprevention of hepatocellular carcinoma: Time to use or wait further?". Clin Mol Hepatol 2024; 30:970-973. [PMID: 38964740 PMCID: PMC11540373 DOI: 10.3350/cmh.2024.0280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 06/25/2024] [Accepted: 07/03/2024] [Indexed: 07/06/2024] Open
Affiliation(s)
- Dorothy Cheuk-Yan Yiu
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
| | - Huapeng Lin
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
| | - Vincent Wai-Sun Wong
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
| | - Grace Lai-Hung Wong
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
| | - Ken Liu
- Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia
| | - Terry Cheuk-Fung Yip
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
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Wang X, Wang J, Li J, Liang K, Dai S, Wang R, Zhang Y, Ren Q, Meng L, Qiu Y. Effect of skeletal muscle index on post-embolization syndrome of hepatocellular carcinoma after transarterial chemoembolization. BMC Gastroenterol 2024; 24:333. [PMID: 39350028 PMCID: PMC11441167 DOI: 10.1186/s12876-024-03427-0] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 09/20/2024] [Indexed: 10/04/2024] Open
Abstract
BACKGROUND Skeletal muscle index (SMI) is a commonly used research method for evaluating muscle mass.However, its impact on post-embolization syndrome(PES) of patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is unclear.Our objective was to determine the effect of SMI on PES after TACE in patients with HCC. METHODS We conducted a retrospective analysis of patients who received TACE treatment for HCC at our hospital from 2015 to 2020. The subjects were divided into two groups according to the presence or absence of PES after TACE, and their clinical characteristics were compared.SMI was measured and calculated by cross-sectionally at the level of the third lumbar vertebra based on computed tomography (CT). According to the cutoff value, the patients were classified into either low or high SMI group.Potential risk factors for PES were assessed using univariate and multivariable Cox proportional risk models. RESULTS A total of 110 people were included in this study, from which including 82 patients experienced PES. Serum albumin was significantly lower in the PES group compared to the non-PES group.The frequency of HCC with a maximum diameter > 3 cm and low SMI in the PES group was significantly higher than in patients without PES. Cox multivariate analysis identified that the maximum diameter of HCC > 3 cm and low SMI were independent predictors of PES after TACE. CONCLUSIONS Low SMI is an independent predictor of PES in HCC patients after TACE treatment, making preoperative CT assessment of skeletal muscle mass is a simple and effective tool for predicting PES.
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Affiliation(s)
- Xiaojuan Wang
- Hebei Provincial Key Laboratory of Portal Hypertension and Cirrhosis, Xingtai People's Hospital, Xingtai, Hebei, 054001, China
| | - Jitao Wang
- Hebei Provincial Key Laboratory of Portal Hypertension and Cirrhosis, Xingtai People's Hospital, Xingtai, Hebei, 054001, China.
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
| | - Jinlong Li
- Hebei Provincial Key Laboratory of Portal Hypertension and Cirrhosis, Xingtai People's Hospital, Xingtai, Hebei, 054001, China
| | - Kuopeng Liang
- Hebei Provincial Key Laboratory of Portal Hypertension and Cirrhosis, Xingtai People's Hospital, Xingtai, Hebei, 054001, China
| | - Shoufang Dai
- Hebei Provincial Key Laboratory of Portal Hypertension and Cirrhosis, Xingtai People's Hospital, Xingtai, Hebei, 054001, China
| | - Ruikun Wang
- Hebei Medical University, Shijiazhuang, Hebei, 050017, China
| | - Yi Zhang
- Hebei Medical University, Shijiazhuang, Hebei, 050017, China
| | - Quan Ren
- Chengde Medical College, Chengde, Hebei, 067000, China
| | - Linglei Meng
- Hebei Provincial Key Laboratory of Portal Hypertension and Cirrhosis, Xingtai People's Hospital, Xingtai, Hebei, 054001, China
| | - Yuzi Qiu
- Hebei Provincial Key Laboratory of Portal Hypertension and Cirrhosis, Xingtai People's Hospital, Xingtai, Hebei, 054001, China
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Tuunanen I, Hautakoski A, Huhtamäki H, Arffman M, Sund R, Puistola U, Karihtala P, Jukkola A, Urpilainen E. The Association of Metformin, Other Antidiabetic Medications, and Statins with the Prognosis of Hepatocellular Carcinoma in Patients with Type 2 Diabetes: A Retrospective Cohort Study. Biomedicines 2024; 12:1654. [PMID: 39200117 PMCID: PMC11351525 DOI: 10.3390/biomedicines12081654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 07/20/2024] [Accepted: 07/22/2024] [Indexed: 09/01/2024] Open
Abstract
This study aimed to explore whether the prediagnostic use of metformin and statins is associated with the prognosis of patients with hepatocellular carcinoma (HCC) and type 2 diabetes. We identified 1383 eligible individuals who had both type 2 diabetes and HCC diagnosed between 1998 and 2017 from several Finnish registers. Cox models were fitted for cause-specific and all-cause mortality in relation to the use of antidiabetic medications and statins prior to the HCC diagnosis. Prediagnostic metformin use was associated with decreased overall mortality (hazard ratio 0.84, 95% confidence interval 0.74-0.94) compared with nonuse in patients with type 2 diabetes. Similarly, slightly decreased HCC mortality and other-cause mortality were observed among metformin users. The results were inconclusive regarding metformin use and both overall and HCC mortality among patients with localized HCC. No discernible contrast between statin users and nonusers was found in overall mortality nor HCC mortality in either the whole cohort or patients with localized cancer.
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Affiliation(s)
- Iida Tuunanen
- Department of Obstetrics and Gynecology, Oulu University Hospital, Wellbeing Services County of North Ostrobothnia, University of Oulu, 90220 Oulu, Finland
- Research Unit of Clinical Medicine, University of Oulu, 90220 Oulu, Finland
- Medical Research Center, Oulu University Hospital, Wellbeing Services County of North Ostrobothnia, University of Oulu, 90220 Oulu, Finland
| | - Ari Hautakoski
- Research Unit of Clinical Medicine, University of Oulu, 90220 Oulu, Finland
- Medical Research Center, Oulu University Hospital, Wellbeing Services County of North Ostrobothnia, University of Oulu, 90220 Oulu, Finland
| | - Heikki Huhtamäki
- Research Unit of Mathematical Sciences, Faculty of Science, University of Oulu, 90014 Oulu, Finland
| | - Martti Arffman
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, 00271 Helsinki, Finland
| | - Reijo Sund
- Institute of Clinical Medicine, University of Eastern Finland, 70029 Kuopio, Finland
| | - Ulla Puistola
- Department of Obstetrics and Gynecology, Oulu University Hospital, Wellbeing Services County of North Ostrobothnia, University of Oulu, 90220 Oulu, Finland
- Research Unit of Clinical Medicine, University of Oulu, 90220 Oulu, Finland
- Medical Research Center, Oulu University Hospital, Wellbeing Services County of North Ostrobothnia, University of Oulu, 90220 Oulu, Finland
| | - Peeter Karihtala
- Department of Oncology, University of Helsinki, Helsinki University Hospital Comprehensive Cancer Center, 00029 Helsinki, Finland
| | - Arja Jukkola
- Department of Oncology and Radiotherapy, Tays Cancer Center, Tampere University Hospital, Faculty of Medicine and Health Technology, Tampere University, 33521 Tampere, Finland;
| | - Elina Urpilainen
- Department of Obstetrics and Gynecology, Oulu University Hospital, Wellbeing Services County of North Ostrobothnia, University of Oulu, 90220 Oulu, Finland
- Research Unit of Clinical Medicine, University of Oulu, 90220 Oulu, Finland
- Medical Research Center, Oulu University Hospital, Wellbeing Services County of North Ostrobothnia, University of Oulu, 90220 Oulu, Finland
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Alfieri CM, Molinari P, Cinque F, Vettoretti S, Cespiati A, Bignamini D, Nardelli L, Fracanzani AL, Castellano G, Lombardi R. What Not to Overlook in the Management of Patients with Type 2 Diabetes Mellitus: The Nephrological and Hepatological Perspectives. Int J Mol Sci 2024; 25:7728. [PMID: 39062970 PMCID: PMC11276657 DOI: 10.3390/ijms25147728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 06/17/2024] [Accepted: 06/22/2024] [Indexed: 07/28/2024] Open
Abstract
Diabetes mellitus (DM) significantly impacts renal and hepatic function, necessitating comprehensive understanding and management strategies. Renal involvement, namely diabetic kidney disease (DKD), presents a global challenge, with increasing prevalence paralleling DM rates. Lifestyle modifications and pharmacotherapy targeting hypertension and glycemic control have pivotal roles in DKD management. Concurrently, hepatic involvement in DM, characterized by metabolic dysfunction-associated steatotic liver disease (MASLD), presents a bidirectional relationship. DM exacerbates MASLD progression, while MASLD predisposes to DM development and worsens glycemic control. Screening for MASLD in DM patients is of high importance, utilizing non-invasive methods like ultrasound and fibrosis scores. Lifestyle modifications, such as weight loss and a Mediterranean diet, mitigate MASLD progression. Promising pharmacotherapies, like SGLT2 inhibitors and GLP-1 agonists, demonstrate efficacy in both DM and MASLD management. Special populations, such as diabetic individuals undergoing hemodialysis or kidney transplant recipients, demand special care due to unique clinical features. Similarly, DM exacerbates complications in MASLD patients, elevating the risks of hepatic decompensation and hepatocellular carcinoma. Recognizing the interconnectedness of DM, renal, and hepatic diseases underscores the need for multidisciplinary approaches for optimal patient outcomes. The present review aims to present the main characteristics and crucial points not to be overlooked regarding the renal and hepatic involvement in DM patients focusing on the inter-relationships between the renal and the hepatic involvements.
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Affiliation(s)
- Carlo Maria Alfieri
- Department of Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Policlinico, 20122 Milan, Italy (L.N.); (G.C.)
- Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy
| | - Paolo Molinari
- Department of Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Policlinico, 20122 Milan, Italy (L.N.); (G.C.)
- Post-Graduate School of Specialization in Nephrology, University of Milan, 20122 Milan, Italy
| | - Felice Cinque
- SC Medicina Indirizzo Metabolico, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, 20122 Milan, Italy; (A.C.); (D.B.); (A.L.F.); (R.L.)
- Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy
| | - Simone Vettoretti
- Department of Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Policlinico, 20122 Milan, Italy (L.N.); (G.C.)
| | - Annalisa Cespiati
- SC Medicina Indirizzo Metabolico, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, 20122 Milan, Italy; (A.C.); (D.B.); (A.L.F.); (R.L.)
- Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy
| | - Daniela Bignamini
- SC Medicina Indirizzo Metabolico, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, 20122 Milan, Italy; (A.C.); (D.B.); (A.L.F.); (R.L.)
| | - Luca Nardelli
- Department of Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Policlinico, 20122 Milan, Italy (L.N.); (G.C.)
- Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy
| | - Anna Ludovica Fracanzani
- SC Medicina Indirizzo Metabolico, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, 20122 Milan, Italy; (A.C.); (D.B.); (A.L.F.); (R.L.)
- Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy
| | - Giuseppe Castellano
- Department of Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Policlinico, 20122 Milan, Italy (L.N.); (G.C.)
- Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy
| | - Rosa Lombardi
- SC Medicina Indirizzo Metabolico, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, 20122 Milan, Italy; (A.C.); (D.B.); (A.L.F.); (R.L.)
- Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy
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9
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Chen TC, Hsiao SW, Chen YY, Yen HH, Su WW, Hsu YC, Huang SP, Su PY. Increased prevalence but decreased survival of nonviral hepatocellular carcinoma compared to viral hepatocellular carcinoma in recent ten years. Sci Rep 2024; 14:9068. [PMID: 38643245 PMCID: PMC11032374 DOI: 10.1038/s41598-024-59668-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 04/12/2024] [Indexed: 04/22/2024] Open
Abstract
Due to the comprehensive hepatitis B virus vaccination program in Taiwan since 1986, the development of antiviral therapy for chronic hepatitis B and chronic hepatitis C infection and covered by National health insurance. Besides, the increased prevalence of nonalcoholic fatty liver disease (NAFLD) and currently, approved therapy for NAFLD remain developing. The etiology of liver-related diseases such as cirrhosis and hepatocellular carcinoma required reinterpretation. This study aimed to analyze the incidence and outcome of hepatocellular carcinoma (HCC) due to viral (hepatitis B and hepatitis C) infection compared to that of nonviral etiology. We retrospectively analyzed patients with HCC from January 2011 to December 2020 from the cancer registry at our institution. Viral-related hepatitis was defined as hepatitis B surface antigen positivity or anti-hepatitis C virus (HCV) antibody positivity. A total of 2748 patients with HCC were enrolled, of which 2188 had viral-related HCC and 560 had nonviral-related HCC. In viral HCC group, the median age at diagnosis was significantly lower (65 years versus 71 years, p < 0.001), and the prevalence of early-stage HCC, including stage 0 and stage A Barcelona Clinic Liver Cancer, was significantly higher (52.9% versus 33.6%, p < 0.001). In nonviral HCC group, alcohol use was more common (39.9% versus 30.1%, p < 0.001), the prevalence of type 2 diabetes mellitus (T2DM) was higher (54.5% versus 35.1%, p < 0.001), and obesity was common (25.0% versus 20.5%, p = 0.026). The prevalence of nonviral HCC increased significantly from 19.2 to 19.3% and 23.0% in the last 10 years (p = 0.046). Overall survival was better in the viral HCC group (5.95 years versus 4.00 years, p < 0.001). In the early stage of HCC, overall survival was still better in the viral HCC group (p < 0.001). The prevalence of nonviral HCC has significantly increased in the last ten years. The overall survival was significantly lower in the nonviral HCC, perhaps because the rate of early HCC detection is lower in nonviral HCC and anti-viral therapy. To detect nonviral HCC early, we should evaluate liver fibrosis in high-risk groups (including people with obesity or T2DM with NAFLD/NASH and alcoholic liver disease) and regular follow-up for those with liver fibrosis, regardless of cirrhosis.
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Affiliation(s)
- Ting-Chun Chen
- Division of Endocrinology and Metabolism, Cheng Ching Hospital, Taichung, Taiwan
| | - Shun-Wen Hsiao
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Yang-Yuan Chen
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan
- Division of Gastroenterology, Yuanlin Christian Hospital, Changhua, Taiwan
- Department of Hospitality Management, MingDao University, Changhua, Taiwan
| | - Hsu-Heng Yen
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Wei-Wen Su
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan
| | - Yu-Chun Hsu
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan
| | - Siou-Ping Huang
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan
| | - Pei-Yuan Su
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan.
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.
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10
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Ayres ABS, Carneiro CRG, Gestic MA, Utrini MP, Chaim FDM, Callejas-Neto F, Chaim EA, Cazzo E. Identification of Predictors of Non-alcoholic Steatohepatitis and Its Severity in Individuals Undergoing Bariatric Surgery. Obes Surg 2024; 34:456-466. [PMID: 38097891 DOI: 10.1007/s11695-023-06986-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 11/28/2023] [Accepted: 12/06/2023] [Indexed: 01/26/2024]
Abstract
BACKGROUND As obesity reached epidemic proportions, non-alcoholic fatty liver disease (NAFLD) also had a worrisome parallel increase. The non-invasive differentiation of non-alcoholic steatohepatitis (NASH) from uncomplicated NAFLD remains an important challenge in current clinical practice. OBJECTIVE To identify predictors of the occurrence and severity of NAFLD and NASH. METHODS This is an analytical cross-sectional study which included individuals undergoing bariatric surgery. Participants were histologically classified according to the presence NASH and severity of NAFLD. Demographic, clinical, anthropometric, and biochemical aspects were analyzed and compared. RESULTS Out of 171 individuals, 87.7% were female and the mean age was 38.4±9.3 years. The average BMI was 38±3.0 kg/m2. NAFLD was histologically confirmed in 74.9%; the commonest histopathological abnormalities were macrovesicular steatosis (74.9%) and ballooning (40.4%). Simple steatosis occurred in 30.4%, 44.4% presented with NASH, and 31% had severe NAFLD. NASH associated with higher levels of ALT (0.03), ALP (0.02), and glucose (0.02). Cutoff values were, respectively, 23 U/L, 67 U/L, and 81 mg/dL. Their concomitant use provided an 83.1% specificity for NASH. Severe NAFLD associated with diabetes (p=0.02), higher BMI (p=0.01), AST (p=0.04), ALT (p<0.01), ALP (p=0.01), glucose (p=0.02), and ferritin (p<0.01). BMI over 39.3 kg/m2 and ferritin over 178 ng/mL concomitantly provided a 70.5% accuracy for severe NAFLD. CONCLUSIONS NASH and severe NAFLD associated with higher levels of ALT, ALP, and glucose. Severe NAFLD associated with higher BMI and higher ferritin levels in this group. The concomitant evaluation of these laboratory tests could help ruling out NASH and safely screening severe NAFLD.
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Affiliation(s)
- Arthur Balestra Silveira Ayres
- Dept. of Surgery-School of Medical Sciences-State University of Campinas (UNICAMP), Rua Alexander Fleming, s/no, Campinas, (SP), Brazil
| | | | - Martinho Antonio Gestic
- Dept. of Surgery-School of Medical Sciences-State University of Campinas (UNICAMP), Rua Alexander Fleming, s/no, Campinas, (SP), Brazil
| | - Murillo Pimentel Utrini
- Dept. of Surgery-School of Medical Sciences-State University of Campinas (UNICAMP), Rua Alexander Fleming, s/no, Campinas, (SP), Brazil
| | - Felipe David Mendonça Chaim
- Dept. of Surgery-School of Medical Sciences-State University of Campinas (UNICAMP), Rua Alexander Fleming, s/no, Campinas, (SP), Brazil
| | - Francisco Callejas-Neto
- Dept. of Surgery-School of Medical Sciences-State University of Campinas (UNICAMP), Rua Alexander Fleming, s/no, Campinas, (SP), Brazil
| | - Elinton Adami Chaim
- Dept. of Surgery-School of Medical Sciences-State University of Campinas (UNICAMP), Rua Alexander Fleming, s/no, Campinas, (SP), Brazil
| | - Everton Cazzo
- Dept. of Surgery-School of Medical Sciences-State University of Campinas (UNICAMP), Rua Alexander Fleming, s/no, Campinas, (SP), Brazil.
- Cidade Universitária Zeferino Vaz, Campinas, (SP), CEP 13085-000, Brazil.
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11
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Lee CH, Mak LY, Tang EHM, Lui DTW, Mak JHC, Li L, Wu T, Chan WL, Yuen MF, Lam KSL, Wong CKH. SGLT2i reduces risk of developing HCC in patients with co-existing type 2 diabetes and hepatitis B infection: A territory-wide cohort study in Hong Kong. Hepatology 2023; 78:1569-1580. [PMID: 37055020 DOI: 10.1097/hep.0000000000000404] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 03/12/2023] [Indexed: 04/15/2023]
Abstract
BACKGROUND AND AIMS Type 2 diabetes (T2D) and chronic hepatitis B infection (CHB) are risk factors of HCC. Sodium glucose co-transporter 2 inhibitors (SGLT2i) inhibit HCC oncogenesis in preclinical studies. However, clinical studies are lacking. This study aimed to evaluate the impact of SGLT2i use on incident HCC using a territory-wide cohort of exclusively patients with co-existing T2D and CHB. APPROACH AND RESULTS Patients with co-existing T2D and CHB between 2015 and 2020 were identified from the representative electronic database of the Hong Kong Hospital Authority. Patients with and without SGLT2i use were 1:1 matched by propensity score for their demographics, biochemistry results, liver-related characteristics, and background medications. Cox proportional hazards regression model was used to assess the association between SGLT2i use and incident HCC. A total of 2,000 patients with co-existing T2D and CHB (1,000 in each SGLT2i and non-SGLT2i group; 79.7% on anti-HBV therapy at baseline) were included after propensity-score matching. Over a follow-up of 3,704 person-years, the incidence rates of HCC were 1.39 and 2.52 cases per 100 person-year in SGLT2i and non-SGLT2i groups, respectively. SGLT2i use was associated with a significantly lower risk of incident HCC (HR 0.54, 95%CI: 0.33-0.88, p =0.013). The association remained similar regardless of sex, age, glycemic control, diabetes duration, presence of cirrhosis and hepatic steatosis, timing of anti-HBV therapy, and background antidiabetic agents including dipeptidyl peptidase-4 inhibitors, insulin, or glitazones (all p interaction>0.05). CONCLUSIONS Among patients with co-existing T2D and CHB, SGLT2i use was associated with a lower risk of incident HCC.
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Affiliation(s)
- Chi-Ho Lee
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China
| | - Lung-Yi Mak
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong SAR, China
| | - Eric Ho-Man Tang
- Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - David Tak-Wai Lui
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Jimmy Ho-Cheung Mak
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Lanlan Li
- Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Tingting Wu
- Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Wing Lok Chan
- Department of Clinical Oncology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Man-Fung Yuen
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong SAR, China
| | - Karen Siu-Ling Lam
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China
| | - Carlos King Ho Wong
- Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong SAR, China
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12
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Llovet JM, Willoughby CE, Singal AG, Greten TF, Heikenwälder M, El-Serag HB, Finn RS, Friedman SL. Nonalcoholic steatohepatitis-related hepatocellular carcinoma: pathogenesis and treatment. Nat Rev Gastroenterol Hepatol 2023; 20:487-503. [PMID: 36932227 PMCID: PMC12165718 DOI: 10.1038/s41575-023-00754-7] [Citation(s) in RCA: 155] [Impact Index Per Article: 77.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/03/2023] [Indexed: 03/19/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD), including its more severe manifestation, nonalcoholic steatohepatitis (NASH), has a global prevalence of 20-25% and is a major public health problem. Its incidence is increasing in parallel to the rise in obesity, diabetes and metabolic syndrome. Progression from NASH to NASH-related hepatocellular carcinoma (HCC) (~2% of cases per year) is influenced by many factors, including the tissue and immune microenvironment, germline mutations in PNPLA3, and the microbiome. NASH-HCC has unique molecular and immune traits compared with other aetiologies of HCC and is equally prevalent in men and women. Comorbidities associated with NASH, such as obesity and diabetes mellitus, can prevent the implementation of potentially curative therapies in certain patients; nonetheless, outcomes are similar in patients who receive treatment. NASH-HCC at the early to intermediate stages is managed with surgery and locoregional therapies, whereas advanced HCC is treated with systemic therapies, including anti-angiogenic therapies and immune-checkpoint inhibitors. In this Review, we present the latest knowledge of the pathogenic mechanisms and clinical management of NASH-HCC. We discuss data highlighting the controversy over varying responses to immune-checkpoint inhibitors according to underlying aetiology and suggest that the future of NASH-HCC management lies in improved surveillance, targeted combination therapies to overcome immune evasion, and identifying biomarkers to recognize treatment responders.
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Affiliation(s)
- Josep M Llovet
- Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Translational Research in Hepatic Oncology, Liver Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain.
- Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain.
| | - Catherine E Willoughby
- Translational Research in Hepatic Oncology, Liver Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain
| | - Amit G Singal
- Department of Internal Medicine, University of Texas Southwestern (UTSW) Medical Centre, Dallas, TX, USA
| | - Tim F Greten
- Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Malignancies Branch, Centre for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA
| | - Mathias Heikenwälder
- Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Hashem B El-Serag
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
- Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA
| | - Richard S Finn
- Department of Medicine, Division of Hematology/Oncology, Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Scott L Friedman
- Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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13
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Kuo YH, Huang TH, Yen YH, Lu SN, Wang JH, Hung CH, Chen CH, Tsai MC, Kee KM. Nomogram to Predict the Long-Term Overall Survival of Early-Stage Hepatocellular Carcinoma after Radiofrequency Ablation. Cancers (Basel) 2023; 15:3156. [PMID: 37370766 DOI: 10.3390/cancers15123156] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Revised: 06/05/2023] [Accepted: 06/09/2023] [Indexed: 06/29/2023] Open
Abstract
Our objective was to develop a predictive nomogram that could estimate the long-term survival of patients with very early/early-stage hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA). For this retrospective study, we enrolled 950 patients who initially received curative RFA for HCC at Barcelona Clinic Liver Cancer (BCLC) stages 0 and A between 2002 and 2016. Factors predicting poor survival after RFA were investigated through a Cox proportional hazard model. The nomogram was constructed using the investigated variables influencing overall survival (OS). After a median follow-up time of 6.25 years, 400 patients had died, and 17 patients had received liver transplantation. The 1-,3-,5-,7-, and 10-year OS rates were 94.5%, 73.5%, 57.9%, 45.7%, and 35.8%, respectively. Multivariate analysis showed that age greater than 65 years, albumin-bilirubin (ALBI) grades 2 and 3, AST-to-platelet ratio index (APRI) greater than 1, tumor size larger than 3 cm, diabetes mellitus, end-stage renal disease, and tumor number greater than 1 were significantly associated with poor OS. The nomogram was constructed using these seven variables. The validation results showed a good concordance index of 0.683. When comparing discriminative ability to tumor, node, and metastasis (TNM), BCLC, and Cancer of the Liver Italian Program (CLIP) staging systems, our nomogram had the highest C-index for predicting mortality. This nomogram provides useful information on prognosis post-RFA as a primary treatment and aids physicians in decision-making.
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Affiliation(s)
- Yuan-Hung Kuo
- Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Tzu-Hsin Huang
- Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Yi-Hao Yen
- Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Sheng-Nan Lu
- Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Jing-Houng Wang
- Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Chao-Hung Hung
- Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Chien-Hung Chen
- Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Ming-Chao Tsai
- Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Kwong-Ming Kee
- Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
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14
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Scherübl H. [Type-2-diabetes and gastrointestinal cancer screening]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:683-689. [PMID: 35697066 DOI: 10.1055/a-1821-9108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
More than 8000000 Germans suffer from diabetes. People with type-2-diabetes (T2D) are at increased risk of gastrointestinal adenocarcinomas. They often develop cancer at younger age and their tumor-specific 5-year-survival is generally shorter. Cancer has become the leading cause of death of T2D-patients. Both chronic hyperglycemia and insulin resistance can stimulate gastrointestinal (GI) tumor growth. T2D can cause colorectal, pancreatic, hepatocellular, biliary and gastric cancer as well as esophageal adenocarcinoma. Both low-risk lifestyle and gastrointestinal cancer screening are effective and reduce GI cancer risk and GI cancer mortality of T2D-patients.
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Affiliation(s)
- Hans Scherübl
- Klinik für Innere Medizin; Gastroenterol., GI Onkol. u. Infektiol., Vivantes Klinikum Am Urban, Berlin, Germany
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15
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Venugopal S, Dhanoa RK, Selvamani TY, Shoukrie SI, Zahra A, Malla J, Selvaraj R, Hamouda RK, Mohammed L. Does Type 2 Diabetes Increase the Risk of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease Patients? A Systematic Review. Cureus 2023; 15:e36079. [PMID: 37065332 PMCID: PMC10101195 DOI: 10.7759/cureus.36079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Accepted: 03/13/2023] [Indexed: 03/14/2023] Open
Abstract
Diabetes is associated with different types of cancers of which hepatocellular carcinoma (HCC) is one among them. In a study comparing patients with diabetes to those who do not have diabetes, it was evident that the risk of HCC is found to increase two-fold in diabetic than that in non-diabetic patients. It is clear that carcinogenesis is advanced due to diabetes in the liver by a variety of mechanisms. We searched PubMed and Google Scholar for articles from 2010 to 2021 that have an association between diabetes, nonalcoholic fatty liver disease (NAFLD), and HCC. For the development of HCC, diabetes is likely related at both the molecular and epidemiological levels. Both diabetes mellitus and hepatic malignancy have the worst impact on mankind socioeconomically. There is a significant relationship between diabetes and HCC independent of alcohol consumption and viral hepatitis. It is noteworthy that not only the elderly but also people of all age groups should monitor their hemoglobin A1C levels. Diet restriction and lifestyle modification can reduce the risk of complications like HCC; the increased physical activity itself can have a major influence on health and can manage comorbidities like diabetes, NAFLD, and HCC.
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Affiliation(s)
- Sathish Venugopal
- Neurology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Ravneet K Dhanoa
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Tharun Yadhav Selvamani
- General Surgery, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Shoukrie I Shoukrie
- Orthopaedics and Traumatology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Anam Zahra
- Surgery, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Jyothirmai Malla
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Ramaneshwar Selvaraj
- Internal Medicine/Family Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- General Surgery, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Ranim K Hamouda
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Lubna Mohammed
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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16
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Vaz J, Strömberg U, Midlöv P, Eriksson B, Buchebner D, Hagström H. Unrecognized liver cirrhosis is common and associated with worse survival in hepatocellular carcinoma: A nationwide cohort study of 3473 patients. J Intern Med 2023; 293:184-199. [PMID: 36166276 PMCID: PMC10091698 DOI: 10.1111/joim.13570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND Data on unrecognized liver cirrhosis in patients with hepatocellular carcinoma (HCC) are derived mainly from cohorts with a risk of selection bias. OBJECTIVES In a population-based cohort study we aimed to determine the proportion, characteristics, and prognosis of HCC in patients with unrecognized cirrhosis. METHODS Using the Swedish quality register for liver cancer and other nationwide registers, we identified all adults with HCC in Sweden between 2012 and 2018 (n = 3,473). RESULTS The final study cohort comprised 2670 patients with established cirrhosis, of which 1033 (39%) had unrecognized cirrhosis at HCC diagnosis. These patients were more often male, older, and had larger tumors, multinodular cancer, portal vein thrombosis, and extrahepatic metastasis compared to patients with known cirrhosis with HCC and under surveillance (34%). Compared to surveilled patients, those with unrecognized cirrhosis had worse median survival (0.89 years, 95% confidence interval [CI] = 0.78-1.01 vs. 3.79 years, 95%CI = 3.19-4.39), and an adjusted hazard ratio of 2.36 (95%CI = 2.09-2.66). Patients with cirrhosis but not under surveillance (27%) and patients with unrecognized cirrhosis had similar characteristics, such as equal proportions diagnosed at late stage (79%). CONCLUSIONS Cirrhosis is often not recognized in patients with HCC. Unrecognized cirrhosis is associated with more advanced HCC at diagnosis and a worse prognosis. More efforts are needed to diagnose cirrhosis at an earlier stage.
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Affiliation(s)
- Juan Vaz
- Department of Clinical Sciences in Malmö, Center for Primary Health Care Research, Lund University, Malmö, Sweden.,Department of Internal Medicine, Halland Hospital Halmstad, Halmstad, Sweden
| | - Ulf Strömberg
- Department of Research and Development, Region Halland, Halmstad, Sweden.,Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Patrik Midlöv
- Department of Clinical Sciences in Malmö, Center for Primary Health Care Research, Lund University, Malmö, Sweden
| | - Berne Eriksson
- Department of Research and Development, Region Halland, Halmstad, Sweden.,Krefting Research Center, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - David Buchebner
- Department of Internal Medicine, Halland Hospital Halmstad, Halmstad, Sweden
| | - Hannes Hagström
- Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.,Division of Hepatology, Department of Upper GI Diseases, Karolinska University Hospital, Stockholm, Sweden.,Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
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17
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Verna EC, Phipps MM, Halazun KJ, Markovic D, Florman SS, Haydel BM, Ruiz R, Klintmalm G, Lee DD, Taner B, Hoteit MA, Tevar AD, Humar A, Chapman WC, Vachharajani N, Aucejo FN, Melcher ML, Nguyen MH, Nydam TL, Markmann JF, Mobley C, Ghobrial RM, Langnas AN, Carol Carney, Berumen J, Schnickel GT, Sudan D, Hong JC, Rana A, Jones CM, Fishbein TM, Busuttil RW, Agopian V. Outcomes in liver transplant recipients with nonalcoholic fatty liver disease-related HCC: results from the US multicenter HCC transplant consortium. Liver Transpl 2023; 29:34-47. [PMID: 36630156 DOI: 10.1097/lvt.0000000000000007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 08/25/2022] [Indexed: 01/12/2023]
Abstract
NAFLD will soon be the most common indication for liver transplantation (LT). In NAFLD, HCC may occur at earlier stages of fibrosis and present with more advanced tumor stage, raising concern for aggressive disease. Thus, adult LT recipients with HCC from 20 US centers transplanted between 2002 and 2013 were analyzed to determine whether NAFLD impacts recurrence-free post-LT survival. Five hundred and thirty-eight (10.8%) of 4981 total patients had NAFLD. Patients with NAFLD were significantly older (63 vs. 58, p<0.001), had higher body mass index (30.5 vs. 27.4, p<0.001), and were more likely to have diabetes (57.3% vs. 28.8%, p<0.001). Patients with NAFLD were less likely to receive pre-LT locoregional therapy (63.6% vs. 72.9%, p<0.001), had higher median lab MELD (15 vs. 13, p<0.001) and neutrophil-lymphocyte ratio (3.8 vs. 2.9, p<0.001), and were more likely to have their maximum pre-LT alpha fetoprotein at time of LT (44.1% vs. 36.1%, p<0.001). NAFLD patients were more likely to have an incidental HCC on explant (19.4% vs. 10.4%, p<0.001); however, explant characteristics including tumor differentiation and vascular invasion were not different between groups. Comparing NAFLD and non-NAFLD patients, the 1, 3, and 5-year cumulative incidence of recurrence (3.1%, 9.1%, 11.5% vs. 4.9%, 10.1%, 12.6%, p=0.36) and recurrence-free survival rates (87%, 76%, and 67% vs. 87%, 75%, and 67%, p=0.97) were not different. In competing risks analysis, NAFLD did not significantly impact recurrence in univariable (HR: 0.88, p=0.36) nor in adjusted analysis (HR: 0.91, p=0.49). With NAFLD among the most common causes of HCC and poised to become the leading indication for LT, a better understanding of disease-specific models to predict recurrence is needed. In this NAFLD cohort, incidental HCCs were common, raising concerns about early detection. However, despite less locoregional therapy and high neutrophil-lymphocyte ratio, explant tumor characteristics and post-transplant recurrence-free survival were not different compared to non-NAFLD patients.
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Affiliation(s)
- Elizabeth C Verna
- Department of Medicine, Division of Digestive and Liver Diseases, Columbia University, New York, New York, USA
| | - Meaghan M Phipps
- Department of Medicine, Division of Digestive and Liver Diseases, Columbia University, New York, New York, USA
| | - Karim J Halazun
- Department of Surgery, Division of Liver Transplantation and Hepatobiliary Surgery, Weill Cornell Medicine, New York, New York, USA
| | - Daniela Markovic
- Department of Biomathematics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Sander S Florman
- Recanati/Miller Transplantation Institute, Mount Sinai Medical Center, New York, New York, USA
| | - Brandy M Haydel
- Recanati/Miller Transplantation Institute, Mount Sinai Medical Center, New York, New York, USA
| | - Richard Ruiz
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, Texas, USA
| | - Goran Klintmalm
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, Texas, USA
| | - David D Lee
- Department of Transplantation, Mayo Clinic, Jacksonville, Florida, USA
| | - Burcin Taner
- Department of Transplantation, Mayo Clinic, Jacksonville, Florida, USA
| | - Maarouf A Hoteit
- Penn Transplant Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Amit D Tevar
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Abhinav Humar
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - William C Chapman
- Section of Transplantation, Department of Surgery, Washington University in St. Louis, St. Louis, Missouri, USA
| | - Neeta Vachharajani
- Section of Transplantation, Department of Surgery, Washington University in St. Louis, St. Louis, Missouri, USA
| | | | - Marc L Melcher
- Department of Surgery, Stanford University, Palo Alto, California, USA
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, California, USA
| | - Trevor L Nydam
- Department of Surgery, Division of Transplant Surgery, University of Colorado School of Medicine, Denver, Colorado, USA
| | - James F Markmann
- Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Constance Mobley
- Sherrie & Alan Conover Center for Liver Disease & Transplantation, Houston Methodist Hospital, Houston, Texas, USA
| | - Rafik M Ghobrial
- Sherrie & Alan Conover Center for Liver Disease & Transplantation, Houston Methodist Hospital, Houston, Texas, USA
| | - Alan N Langnas
- Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Carol Carney
- Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Jennifer Berumen
- Department of Surgery, Division of Transplantation and Hepatobiliary Surgery, University of California, San Diego, California, USA
| | - Gabriel T Schnickel
- Department of Surgery, Division of Transplantation and Hepatobiliary Surgery, University of California, San Diego, California, USA
| | - Debra Sudan
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
| | - Johnny C Hong
- Department of Surgery, Division of Transplant Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Abbas Rana
- Department of Surgery, Baylor College of Medicine, Houston, Texas, USA
| | - Christopher M Jones
- Section of Hepatobiliary and Transplant Surgery, University of Louisville School of Medicine, Louisville, Kentucky, USA
| | - Thomas M Fishbein
- Medstar Georgetown Transplant Institute, Georgetown University, Washington, District of Columbia, USA
| | - Ronald W Busuttil
- Department of Surgery, Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Centers, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Vatche Agopian
- Department of Surgery, Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Centers, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
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18
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Nakatsuka T, Tateishi R. Development and prognosis of hepatocellular carcinoma in patients with diabetes. Clin Mol Hepatol 2023; 29:51-64. [PMID: 35903020 PMCID: PMC9845683 DOI: 10.3350/cmh.2022.0095] [Citation(s) in RCA: 40] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 07/03/2022] [Indexed: 02/02/2023] Open
Abstract
The incidence of diabetes mellitus and hepatocellular carcinoma (HCC) has been increasing worldwide during the last few decades, in the context of an increasing prevalence of obesity and non-alcoholic fatty liver disease (NAFLD). Epidemiologic studies have revealed that patients with diabetes have a 2- to 3-fold increased risk of developing HCC, independent of the severity and cause of the underlying liver disease. A bidirectional relationship exists between diabetes and liver disease: advanced liver disease promotes the onset of diabetes, and HCC is an important cause of death in patients with diabetes; conversely, diabetes is a risk factor for liver fibrosis progression and HCC development, and may worsen the long-term prognosis of patients with HCC. The existence of close interconnections among diabetes, obesity, and NAFLD causes insulin resistance-related hyperinsulinemia, increased oxidative stress, and chronic inflammation, which are assumed to be the underlying causes of hepatocarcinogenesis in patients with diabetes. No appropriate surveillance methods for HCC development in patients with diabetes have been established, and liver diseases, including HCC, are often overlooked as complications of diabetes. Although some antidiabetic drugs are expected to prevent HCC development, further research on the optimal use of antidiabetic drugs aimed at hepatoprotection is warranted. Given the increasing medical and socioeconomic impact of diabetes on HCC development, diabetologists and hepatologists need to work together to develop strategies to address this emerging health issue. This article reviews the current knowledge on the impact of diabetes on the development and progression of HCC.
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Affiliation(s)
- Takuma Nakatsuka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryosuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan,Corresponding author : Ryosuke Tateishi Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan Tel: +81-3-3815-5411, Fax: +81-3-3814-0021, E-mail:
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19
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Fu J, Jiang J, Liu K. Metabolic syndrome and survival of patients with hepatocellular carcinoma: A meta-analysis. Front Oncol 2023; 13:1117846. [PMID: 36910647 PMCID: PMC9995822 DOI: 10.3389/fonc.2023.1117846] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Accepted: 01/04/2023] [Indexed: 02/25/2023] Open
Abstract
Background Metabolic syndrome (MetS) has been related to a high incidence of hepatocellular carcinoma (HCC). However, the influence of MetS on survival of patients with HCC is still unclear. We performed a systematic review and meta-analysis to evaluate the association between MetS and survival of HCC patients. Methods A search of PubMed, Embase, and Web of Science retrieved relevant cohort studies from the inception of the databases to October 16, 2022. Data collection, literature search, and statistical analysis were carried out independently by two authors. We pooled the results using a random-effects model that incorporates heterogeneity. Results In the meta-analysis, 8080 patients with HCC were included from ten cohort studies, and 1166 patients (14.4%) had MetS. Eight studies included patients treated primarily with radical hepatectomy, one study with patients receiving sorafenib, and another study included patients who were treated with radical hepatectomy or non-surgical treatments. Pooled results showed that MetS was associated with poor overall survival (OS, risk ratio [RR]: 1.21, 95% confidence interval [CI]:1.08 to 1.37, p = 0.001; I2 = 32%) and progression-free survival (PFS, RR: 1.33, 95% CI: 1.18 to 1.49, p < 0.001, I2 = 14%). Influencing analysis by excluding one study at a time showed consistent results (p all < 0.05). Subgroup analyses showed similar results in studies with MetS diagnosed with the National Cholesterol Education Program Adult Treatment Panel III or International Diabetes Federal criteria, and in studies with mean follow-up durations < or ≥ 3.5 years (p for subgroup difference all > 0.05). Conclusion In patients with HCC, MetS may be a risk factor of poor OS and PFS, particularly for those after radical hepatectomy.
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Affiliation(s)
- Jia Fu
- Department of Oncology, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Hunan Normal University, Changsha, China
| | - Jinqiong Jiang
- Department of Oncology, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Hunan Normal University, Changsha, China
| | - Kanghan Liu
- Department of Nephrology and Laboratory of Kidney Disease, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Hunan Normal University, Hunan Clinical Research Center for Chronic Kidney Disease, Changsha, China
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20
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Hendryx M, Dong Y, Ndeke JM, Luo J. Sodium-glucose cotransporter 2 (SGLT2) inhibitor initiation and hepatocellular carcinoma prognosis. PLoS One 2022; 17:e0274519. [PMID: 36094949 PMCID: PMC9467321 DOI: 10.1371/journal.pone.0274519] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Accepted: 08/29/2022] [Indexed: 11/18/2022] Open
Abstract
Introduction
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of antidiabetic drugs. Emerging findings from laboratory studies indicate that SGLT2 inhibitors can improve liver function and suppress the proliferation of hepatocellular carcinoma (HCC) cells. The aim of this study was to test the hypothesis that initiation of SGLT2 inhibitors improves HCC prognosis in a human population.
Methods
We used National Surveillance, Epidemiology and End Results (SEER)—Medicare linked data in the United States to evaluate the role of SGLT2 inhibitor initiation on the survival of HCC patients. 3,185 HCC patients newly diagnosed between 2014 and 2017 aged 66 years or older with pre-existing type 2 diabetes were included and followed to the end of 2019. Information on SGLT2 inhibitor initiation was extracted from the Medicare Part D file.
Results
SGLT2 inhibitor initiation was associated with significantly lower mortality risk after adjusting for potential confounders (HR = 0.68, 95% CI = 0.54–0.86) with stronger association for longer duration of use (HR = 0.60, 95% CI = 0.41–0.88). Further, we found that SGLT2 inhibitor initiation was associated with a lower risk mortality risk ranging from 14% to 60% regardless of patient demographic variables, tumor characteristics, and cancer treatments.
Conclusion
Our large SEER-Medicare linked data study indicates that SGLT2 inhibitor initiation was associated with improved overall survival of HCC patients with pre-existing type 2 diabetes compared with no SGLT2 inhibitor use. Further studies are needed to confirm our findings and elucidate the possible mechanisms behind the association.
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Affiliation(s)
- Michael Hendryx
- Department of Environmental and Occupational Health, School of Public Health, Indiana University, Bloomington, Indiana, United States of America
- * E-mail:
| | - Yi Dong
- Indiana University Simon Cancer Center, Indianapolis, Indiana, United States of America
- Division of Hematology Oncology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America
| | - Jonas M. Ndeke
- Department of Epidemiology and Biostatistics, School of Public Health, Indiana University, Bloomington, Indiana, United States of America
| | - Juhua Luo
- Department of Epidemiology and Biostatistics, School of Public Health, Indiana University, Bloomington, Indiana, United States of America
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21
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Pinyopornpanish K, Al-Yaman W, Dasarathy S, Romero-Marrero C, McCullough A. Hepatocellular Carcinoma in Patients Without Cirrhosis: The Fibrosis Stage Distribution, Characteristics and Survival. Dig Dis Sci 2022; 67:2677-2687. [PMID: 34027591 PMCID: PMC9087017 DOI: 10.1007/s10620-021-07048-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 05/09/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND The data on hepatocellular carcinoma (HCC) patients without liver cirrhosis is scarce. AIMS To study the epidemiology, underlying etiology and fibrosis distribution in noncirrhotic HCC and compare the survival outcomes to cirrhotic HCC. METHODS We conducted a retrospective study including all adult patients diagnosed with HCC at two US tertiary academic centers from 2000 to 2015. Univariable and multivariable Cox regression analyses were performed to evaluate the variables associated with patient survival. RESULTS Two thousand two hundred and thirty-seven HCC patients were included in the final analysis, of which, 13% had no liver cirrhosis. The most common underlying liver disease in non-cirrhotic patients was cryptogenic cause (40%), followed by nonalcoholic fatty liver disease (NAFLD) (25.2%) and hepatitis C (19%). The percentage of F0-F1, F2, and F3 was 72%, 17%, and 11% (cryptogenic cause); 69%, 12%, and 19% (NAFLD); 50%, 17%, and 33% (alcohol); 33%, 39%, and 28% (hepatitis B); 20%, 40%, and 40% (hemochromatosis); and 12%, 40%, and 48% (hepatitis C), respectively. In non-cirrhotic compared to cirrhotic patients, the tumor was more likely to be larger and fell outside Milan criteria (all p < 0.001). Cirrhotic patients had significant shorter survival than non-cirrhotic patients (p < 0.001). On the multivariable analysis, having liver cirrhosis (HR 1.48; 1.21-1.82, p < 0.001), combined viral hepatitis and alcohol use (HR 1.51; 1.23-1.88, p < 0.001), morbid obesity (HR 1.31; 1.01-1.69, p = 0.040) and underweight (HR 2.06; 1.27-3.34, p = 0.004) were associated with worse patient survival. CONCLUSIONS The fibrosis distribution in non-cirrhotic HCC differed among each etiology of liver diseases. Despite more advanced HCC, patients without cirrhosis had significantly longer survival than those with cirrhosis.
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Affiliation(s)
- Kanokwan Pinyopornpanish
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
| | - Wael Al-Yaman
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Srinivasan Dasarathy
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
- Department of Immunity and Inflammation, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Carlos Romero-Marrero
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Arthur McCullough
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
- Department of Immunity and Inflammation, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
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22
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Scherübl H. Krebsrisiko bei Prädiabetes und Typ-2-Diabetes mellitus. DIABETOL STOFFWECHS 2022. [DOI: 10.1055/a-1837-2035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
ZusammenfassungKrebs ist nun die führende Todesursache bei Typ-2-Diabetes mellitus (T2D). Prädiabetes und T2D erhöhen das Risiko für bestimmte Tumoren. Zu den Prädiabetes- bzw. T2D-assoziierten Malignomen zählen gastrointestinale, gynäkologische, urologische und endokrine Karzinome aber auch Leukämien. Prädiabetes und T2D bedingen eine 1,2- bis 2,7-fach erhöhte Krebssterblichkeit. Zugrundeliegende Mechanismen der Assoziation zwischen T2D und Krebs beinhalten die chronische Hyperglykämie, einen chronischen systemischen Entzündungszustand, oxidativen Stress, Dyslipidämie, die Insulinresistenz sowie chronisch erhöhte Spiegel von insulin-like growth factor 1 (IGF-1) und von Insulin. Eine dauerhafte Gewichtsreduktion kann das Krebsrisiko adipöser T2D-Patienten signifikant senken. Ein gesunder Lebensstil und die regelmäßige Teilnahme an Vorsorgeuntersuchungen sind wichtig und können die Krebsmortalität von Diabetespatienten erheblich verringern.
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Affiliation(s)
- Hans Scherübl
- Klinik für Innere Medizin, Gastroenterologie, GI Onkologie, Diabetologie und Infektiologie, Vivantes Netzwerk für Gesundheit GmbH, Berlin, Germany
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23
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Cao JZ, Wang ZG, Yu J, Tao YP, Yang Y, Liu H, Zhou WP, Lu J, Huang Q. Antidiabetic treatment improves prognosis after radical resection in hepatocellular carcinoma patients with diabetes mellitus: a retrospective cohort study from 2000 to 2013. J Gastrointest Oncol 2022; 13:1330-1339. [PMID: 35837203 PMCID: PMC9274028 DOI: 10.21037/jgo-22-478] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 06/14/2022] [Indexed: 01/04/2025] Open
Abstract
BACKGROUND It remains unclear whether diabetic medications, such as metformin and insulin, affect the post-liver resection prognosis of hepatocellular carcinoma (HCC) patients complicated with diabetes mellitus (DM). This study try to find out the prognostic factors in HCC patients with DM and provide a better antidiabetic therapy after liver resection. METHODS Patients presenting with HCC complicated with DM undergoing liver resection were enrolled in this study. They were examined and followed up every 3-6 months after surgery. Patients were divided into the antidiabetic treatment group and no antidiabetic treatment group according to whether they received medications for diabetes or not. Then patients in the antidiabetic treatment group were further divided into insulin group, metformin group, insulin plus metformin group and others group, according to the medications they received. Overall survival (OS) and recurrence-free survival (RFS) were compared among two groups and four subgoups. Comparative and multivariate analyses were performed to investigate the effects of DM medication on the prognosis of these HCC patients, using Cox proportional hazards model. RESULTS The 1-, 3-, 5-, and 7-year OS rates for the antidiabetic treatment group were 87.5%, 75.5%, 48.7%, and 29.1%, respectively, and for the no antidiabetic treatment group, the OS rates were 85.4%, 57.7%, 33.6%, and 19.1%, respectively (P=0.007). The 1-, 3-, 5-, 7-year RFS rates for the antidiabetic treatment group were 76.4%, 53.5%, 28.5%, and 17.5%, respectively, and for the no antidiabetic treatment group, the RFS rates were 69.5%, 32.5%, 16.5%, and 10.7%, respectively (P=0.001). In subgroup analysis, There was no significant difference in either RFS (P=0.934) nor OS (P=0.412) among the different types of antidiabetic treatment regimens. Cox proportional hazard regression analysis revealed that tumor size (HR: 1.048), tumor number (HR: 1.626), vascular invasion (HR: 2.074, P=0.003), satellite tumor (HR: 1.592), Edmondson classification (HR: 1.468) and antidiabetic treatment (HR: 0.722) were independent prognostic factors of DFS, while tumor size (HR: 1.048), tumor number (HR: 1.779), vascular invasion (HR: 2.545), Edmondson classification (HR: 1.596) and antidiabetic treatment (HR: 0.713) were independent prognostic factors of OS. CONCLUSIONS For HCC patients with DM, antidiabetic treatment should be recommended aggressively in order to improve the surgical outcome, regardless of which antidiabetic drugs are used.
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Affiliation(s)
- Jing-Zhu Cao
- Department of Endocrinology, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Zhen-Guang Wang
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
- National Liver Tissue Bank, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Jian Yu
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
- National Liver Tissue Bank, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Yuan-Ping Tao
- National Liver Tissue Bank, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Yuan Yang
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
- National Liver Tissue Bank, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Hui Liu
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
- National Liver Tissue Bank, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Wei-Ping Zhou
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
- National Liver Tissue Bank, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Jin Lu
- Department of Endocrinology, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Qin Huang
- Department of Endocrinology, Changhai Hospital, Naval Medical University, Shanghai, China
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24
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Shen GL, Lu Y, Liang L, Lu WF, Diao YK, Xiao ZQ, Zhang KJ, Zhang JG, Zhang CW, Liu J. Impact of diabetes mellitus on the long-term prognosis of patients with hepatocellular carcinoma after hepatectomy. Expert Rev Gastroenterol Hepatol 2022; 16:473-478. [PMID: 35387530 DOI: 10.1080/17474124.2022.2063837] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The impact of diabetes mellitus (DM) on the survival of patients with hepatocellular carcinoma (HCC) is still unclear. The present study aims to draw a firm conclusion in terms of evaluating the impact of DM on the prognosis of HCC after hepatectomy. METHODS The pattern of recurrence for HCC was often stratified into early-stage (<2 years) and late-stage (≥2 years) recurrence. Because the early-stage recurrence was mainly attributed to aggressive tumor pathological characteristics, patients who recurrence or die within 2 years were excluded. Cumulative overall survival (OS) and recurrence-free survival (RFS) were determined by the method of Kaplan-Meier, and the independent risk factors of OS/RFS were determined by Cox regression analysis. RESULTS A total of 426 patients were eventually included. The 3- and 5-year OS in patients with and without DM was 83.7%, 55.1%; and 90.9%, 77.4%, respectively. Multivariate analysis showed that DM was an independent risk factor for OS (HR 1.166, 95% CI 1.056-2.036, P = 0.022) and RFS (HR 1.365, 95% CI 1.043-1.787, P = 0.023). CONCLUSION DM is an independent risk factor for long-term prognosis in patients with HCC. Patients with DM after hepatectomy for HCC, thus, need to actively control DM and closer follow-up.
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Affiliation(s)
- Guo-Liang Shen
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Yi Lu
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Lei Liang
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.,Department of Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou, China
| | - Wen-Feng Lu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, Zhejiang, China
| | - Yong-Kang Diao
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Zun-Qiang Xiao
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Kang-Jun Zhang
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Jun-Gang Zhang
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Cheng-Wu Zhang
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Junwei Liu
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
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Long-Term Survival Impact of High-Grade Complications after Liver Resection for Hepatocellular Carcinoma: A Retrospective Single-Centre Cohort Study. Medicina (B Aires) 2022; 58:medicina58040534. [PMID: 35454372 PMCID: PMC9024755 DOI: 10.3390/medicina58040534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 04/05/2022] [Accepted: 04/11/2022] [Indexed: 01/27/2023] Open
Abstract
Background and Objectives: Although complications after liver resection for hepatic cancer are common, the long-term impact of these complications on oncological outcomes remains unclear. This study aimed to investigate the potential effect of high-grade postoperative complications on long-term mortality and cancer recurrence after surgical resection of hepatocellular carcinoma. Materials and Methods: In a retrospective cohort study, patients undergoing curative liver resection for primary hepatocellular carcinoma between 2005 and 2016 were evaluated. The Clavien–Dindo (CD) grading system was used to classify patients into two groups of either high-grade complications (grade III or IV) or none or low-grade complications (grade 0 to II) within 30 days after surgery. The primary endpoint was all-cause mortality. Secondary endpoints were cancer-specific mortality and cancer recurrence. Weighted Cox proportional hazards regression models were used to calculate the adjusted hazard ratio (aHR) with a 95% confidence interval (CI) for the outcomes of interest. Results: A total of 1419 patients with a median follow-up time of 46.6 months were analysed. Among them, 93 (6.6%) developed high-grade complications after surgery. The most common complications were bile leakage (n = 30) in CD grade III and respiratory failure (n = 13) in CD grade IV. High-grade complications were significantly associated with all-cause mortality (aHR: 1.78, 95% CI: 1.55–2.06) and cancer-specific mortality (aHR: 1.34, 95% CI: 1.13–1.60), but not cancer recurrence (aHR: 0.92, 95% CI: 0.84–1.02). Independent influential factors for complications were sex, diabetes mellitus, clinically significant portal hypertension, oesophageal varices, multifocal cancer, intraoperative blood loss, and anaesthesia duration. Conclusions: Patients who had high-grade postoperative complications had a greater risk of long-term mortality after liver resection for hepatocellular carcinoma. Prevention of postoperative complications may serve as an effective strategy for improving long-term survival.
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Cisneros-Garza L, González-Huezo M, Moctezuma-Velázquez C, Ladrón de Guevara-Cetina L, Vilatobá M, García-Juárez I, Alvarado-Reyes R, Álvarez-Treviño G, Allende-Pérez S, Bornstein-Quevedo L, Calderillo-Ruiz G, Carrillo-Martínez M, Castillo-Barradas M, Cerda-Reyes E, Félix-Leyva J, Gabutti-Thomas J, Guerrero-Ixtlahuac J, Higuera-de-la-Tijera F, Huitzil-Meléndez D, Kimura-Hayama E, López-Hernández P, Malé-Velázquez R, Méndez-Sánchez N, Morales-Ruiz M, Ruíz-García E, Sánchez-Ávila J, Torrecillas-Torres L. The second Mexican consensus on hepatocellular carcinoma. Part I: Epidemiology and diagnosis. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2022; 87:216-234. [DOI: 10.1016/j.rgmxen.2021.10.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 10/21/2021] [Indexed: 12/24/2022] Open
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Cisneros-Garza LE, González-Huezo MS, Moctezuma-Velázquez C, Ladrón de Guevara-Cetina L, Vilatobá M, García-Juárez I, Alvarado-Reyes R, Álvarez-Treviño GA, Allende-Pérez S, Bornstein-Quevedo L, Calderillo-Ruiz G, Carrillo-Martínez MA, Castillo-Barradas M, Cerda-Reyes E, Félix-Leyva JA, Gabutti-Thomas JA, Guerrero-Ixtlahuac J, Higuera-de-la-Tijera F, Huitzil-Meléndez D, Kimura-Hayama E, López-Hernández PA, Malé-Velázquez R, Méndez-Sánchez N, Morales-Ruiz MA, Ruíz-García E, Sánchez-Ávila JF, Torrecillas-Torres L. The second Mexican consensus on hepatocellular carcinoma. Part I: Epidemiology and diagnosis. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2022; 87:216-234. [PMID: 35431142 DOI: 10.1016/j.rgmx.2021.10.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 10/21/2021] [Indexed: 01/04/2025]
Abstract
Hepatocellular carcinoma (HCC) is more frequently manifesting as one of the main complications of cirrhosis of the liver, its principal risk factor. There have been modifications in its incidence over the past decade, related to an epidemiologic transition in the etiology of cirrhosis, with a decrease in the prevalence of hepatitis C and an increase in nonalcoholic fatty liver disease (NAFLD) as a cause, as well as the development of HCC in the non-cirrhotic liver due to NAFLD. Genetic markers associated with the disease have been identified, and surveillance and diagnosis have improved. Regarding treatment, surgical techniques, in both resection and transplantation, have advanced and radiologic techniques, at the curative stage of the disease, have enhanced survival in those patients. And finally, there have been radical changes in the systemic approach, with much more optimistic expectations, when compared with the options available a decade ago. Therefore, the Asociación Mexicana de Hepatología decided to carry out the Second Mexican Consensus on Hepatocellular Carcinoma, which is an updated review of the available national and international evidence on the epidemiology, risk factors, surveillance, diagnosis, and treatment of the disease, to offer the Mexican physician current information on the different topics regarding hepatocellular carcinoma. In this first part of the document, the topics related to epidemiology and diagnosis are presented.
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Affiliation(s)
- L E Cisneros-Garza
- Hospital Christus Muguerza Alta Especialidad, Monterrey, Nuevo León, Mexico
| | | | - C Moctezuma-Velázquez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | - M Vilatobá
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - I García-Juárez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | - G A Álvarez-Treviño
- Unidad de Medicina de Alta Especialidad 25 IMSS, Monterrey, Nuevo León, Mexico
| | | | - L Bornstein-Quevedo
- InmunoQ, Laboratorio de Patología, Inmunohistoquímica y Biología Molecular, Mexico City, Mexico
| | | | | | | | | | | | - J A Gabutti-Thomas
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | - D Huitzil-Meléndez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | - P A López-Hernández
- Unidad de Medicina de Alta Especialidad 25 IMSS, Monterrey, Nuevo León, Mexico
| | - R Malé-Velázquez
- Instituto de Salud Digestiva y Hepática SA de CV, Guadalajara, Jalisco, Mexico
| | | | - M A Morales-Ruiz
- Centro Oncológico Estatal Issemym, Toluca, Estado de México, Mexico
| | - E Ruíz-García
- Instituto Nacional de Cancerología, Mexico City, Mexico
| | - J F Sánchez-Ávila
- Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey, Nuevo León, Mexico
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He TT, Xiao H, Wusiman M, Yishake D, Fang AP, Luo Y, Liu XZ, Liu ZY, Zhu HL. Dietary intake of one-carbon metabolism-related nutrients and hepatocellular carcinoma survival in the Guangdong Liver Cancer Cohort. Food Funct 2022; 13:8081-8090. [DOI: 10.1039/d2fo00943a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Dietary intake of one-carbon metabolism-related nutrients has been linked to cancer-related outcomes, but their effects on hepatocellular carcinoma (HCC) mortality are still unknown. The objective was to assess whether pre-diagnostic...
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Fan Z, Wu M, Tang Z, He A, Liu F, Liang W, Wang Z, Yang D. Predictive Value of Platelet-Related Measures in Patients with Hepatocellular Carcinoma. Technol Cancer Res Treat 2022; 21:15330338211064414. [PMID: 35225081 PMCID: PMC8891878 DOI: 10.1177/15330338211064414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background: Increasing numbers of studies reported platelet (PLT)- related measures could play a creative role in many malignancies, while the prognostic impact of these measures in hepatocellular carcinoma (HCC) remains limited and controversial. It is worth exploring the predictive value of PLT-related measures in HCC. Methods: A total of 279 HCC patients with hepatectomy were analyzed in the retrospective cohort study. The optimal cut-off points of these PLT-related indices were obtained by the receiver operating characteristic (ROC) curve. The associations of these indices with clinical characteristics and overall survival (OS) were evaluated by Kaplan–Meier curves and Cox proportional hazards models. Results: High PLT count and low prognostic nutritional index (low-PNI) were significantly associated with larger tumor size. The low gamma-glutamyl transpeptidase-to-platelet ratio (low-GPR) group was inclined to more hepatitis infections. Survival curves indicated that preoperative high-PLT, low-GPR, and low-PNI had a worse prognosis after surgery in the cohort. In addition, PLT≥220 × 109/L (HR, 2.274; 95% CI, 1.061-4.876; P = .035), PNI≥51.9 (HR, 0.503; 95% CI, 0.265-0.954; P = .035), and GPR≥0.2 (HR, 0.432; 95% CI, 0.204-0.912; P = .028) were identified as independent prognostic factors for survival outcomes in the multivariable analysis. Conclusion: High-PLT, low-GPR, and low-PNI as the preoperative predictors were associated with poor OS in HCC patients with hepatectomy. Our data reveal that they could be simple, easily obtained, and effective predictors for evaluation of survival outcomes in patients.
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Affiliation(s)
- Zhijia Fan
- Huashan Hospital, 159397Fudan University, Shanghai, China
| | - Mengmeng Wu
- Huashan Hospital, 159397Fudan University, Shanghai, China
| | - Zihui Tang
- Huashan Hospital, 159397Fudan University, Shanghai, China
| | - Anfang He
- Huashan Hospital, 159397Fudan University, Shanghai, China
| | - Fuchen Liu
- 535219Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Wei Liang
- The Second People's Hospital of Lianyungang City, Jiangsu Province, China
| | - Zhicheng Wang
- Huashan Hospital, 159397Fudan University, Shanghai, China
| | - Dongqin Yang
- Huashan Hospital, 159397Fudan University, Shanghai, China
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Grattagliano I, Rossi A, Marconi E, Lapi F, Cricelli C. Determinants of HCV-related complications in Italian primary care patients. Liver Int 2021; 41:2857-2865. [PMID: 34268863 DOI: 10.1111/liv.15017] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 06/01/2021] [Accepted: 07/05/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIMS This study aimed to assess the demographic and clinical determinants of liver complications in Hepatitis C virus (HCV)-positive patients in primary care setting. METHODS Using the Health Search database, we selected a cohort of patients aged ≥14 diagnosed with HCV between 2002 and 2017. Patients were followed up until the occurrence of cirrhosis and other disease progressions such as oesophageal varices, hepatocellular carcinoma and/or liver transplantation. The candidate determinants for the risk of HCV-related complications included sex, age, smoking status, liver fibrosis (measured by fibrosis 4 index [FIB-4]), infections by the human immunodeficiency virus (HIV), hepatitis B virus (HBV), other forms of hepatitis, abuse of alcohol or illicit substances or drugs, obesity, metabolic syndrome, diabetes mellitus and renal disease. Cox regression was used to test the association between candidate determinants and the outcome. RESULTS The cohort included 8299 HCV-positive patients (50.93% men) with an overall prevalence rate equal to 0.61%. At least one HCV-related complication was found in 12.2% of patients, with a mean time-to-event equal to 8.1 year. Along with male sex and advanced age, a FIB-4 greater than 3.25 and the presence of diabetes were associated with a greater risk of HCV-related complications. CONCLUSION Our study shows that patients with certain demographics and clinical characteristics are more prone to incur in HCV-related complications. The knowledge and early identification of these determinants by GPs may result in reducing disease progression and related healthcare costs through a closer monitoring.
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Affiliation(s)
| | - Alessandro Rossi
- Italian College of General Practitioners and Primary Care, Florence, Italy
| | - Ettore Marconi
- Health Search, Italian College of General Practitioners and Primary Care, Florence, Italy
| | - Francesco Lapi
- Health Search, Italian College of General Practitioners and Primary Care, Florence, Italy
| | - Claudio Cricelli
- Italian College of General Practitioners and Primary Care, Florence, Italy
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Konyn P, Ahmed A, Kim D. Current epidemiology in hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2021; 15:1295-1307. [PMID: 34624198 DOI: 10.1080/17474124.2021.1991792] [Citation(s) in RCA: 159] [Impact Index Per Article: 39.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 10/07/2021] [Indexed: 01/27/2023]
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third-leading cause of cancer-related mortality in the world. AREAS COVERED This review will discuss risk factors, demographic differences, global trends, and the economic burden of HCC. Viral hepatitis, particularly hepatitis B virus (HBV) infection, is the most common underlying liver disease leading to HCC in those with cirrhosis. Other important risk factors include alcoholic liver disease, nonalcoholic fatty liver disease, metabolic syndrome, etc. With the introduction of direct-acting antiviral agents for hepatitis C virus infection, routine vaccination against HBV, and increasing support for robust public screening programs, the incidence rates for HCC due to viral hepatitis is falling in many countries. Meanwhile, the prevalence of obesity and metabolic syndrome are on the rise, as is NAFLD-related HCC incidence. Asia and Africa have the highest incidence rates of HCC. In multiethnic countries, racial and ethnic minorities experience disparities in HCC incidence as well as mortality, representing an essential area for improvement in terms of healthcare inequity. EXPERT OPINION Interventions to minimize the global burden of HCC aim to reduce rates of the most common risk factors and implement effective treatment of underlying etiology and comprehensive screening programs for HCC.
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Affiliation(s)
- Peter Konyn
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
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Alexopoulos A, Crowley MJ, Wang Y, Moylan CA, Guy CD, Henao R, Piercy DL, Seymour KA, Sudan R, Portenier DD, Diehl AM, Coviello AD, Abdelmalek MF. Glycemic Control Predicts Severity of Hepatocyte Ballooning and Hepatic Fibrosis in Nonalcoholic Fatty Liver Disease. Hepatology 2021; 74:1220-1233. [PMID: 33724511 PMCID: PMC8518519 DOI: 10.1002/hep.31806] [Citation(s) in RCA: 88] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 02/09/2021] [Accepted: 03/01/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Whether glycemic control, as opposed to diabetes status, is associated with the severity of NAFLD is open for study. We aimed to evaluate whether degree of glycemic control in the years preceding liver biopsy predicts the histological severity of NASH. APPROACH AND RESULTS Using the Duke NAFLD Clinical Database, we examined patients with biopsy-proven NAFLD/NASH (n = 713) and the association of liver injury with glycemic control as measured by hemoglobin A1c (HbA1c). The study cohort was predominantly female (59%) and White (84%) with median (interquartile range) age of 50 (42, 58) years; 49% had diabetes (n = 348). Generalized linear regression models adjusted for age, sex, race, diabetes, body mass index, and hyperlipidemia were used to assess the association between mean HbA1c over the year preceding liver biopsy and severity of histological features of NAFLD/NASH. Histological features were graded and staged according to the NASH Clinical Research Network system. Group-based trajectory analysis was used to examine patients with at least three HbA1c (n = 298) measures over 5 years preceding clinically indicated liver biopsy. Higher mean HbA1c was associated with higher grade of steatosis and ballooned hepatocytes, but not lobular inflammation. Every 1% increase in mean HbA1c was associated with 15% higher odds of increased fibrosis stage (OR, 1.15; 95% CI, 1.01, 1.31). As compared with good glycemic control, moderate control was significantly associated with increased severity of ballooned hepatocytes (OR, 1.74; 95% CI, 1.01, 3.01; P = 0.048) and hepatic fibrosis (HF; OR, 4.59; 95% CI, 2.33, 9.06; P < 0.01). CONCLUSIONS Glycemic control predicts severity of ballooned hepatocytes and HF in NAFLD/NASH, and thus optimizing glycemic control may be a means of modifying risk of NASH-related fibrosis progression.
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Affiliation(s)
- Anastasia‐Stefania Alexopoulos
- Division of EndocrinologyDepartment of MedicineDuke UniversityDurham,NC
- Durham Veterans Affairs Center of Innovation to Accelerate Discovery and Practice Transformation (ADAPT)DurhamNC
| | - Matthew J. Crowley
- Division of EndocrinologyDepartment of MedicineDuke UniversityDurham,NC
- Durham Veterans Affairs Center of Innovation to Accelerate Discovery and Practice Transformation (ADAPT)DurhamNC
| | - Ying Wang
- Division of GastroenterologyDepartment of MedicineDuke UniversityDurham,NC
| | - Cynthia A. Moylan
- Division of GastroenterologyDepartment of MedicineDuke UniversityDurham,NC
- Division of GastroenterologyDurham Veterans Affairs Medical CenterDurhamNC
| | | | - Ricardo Henao
- Division of Biostatistics and BioinformaticsDuke UniversityDurhamNC
| | - Dawn L. Piercy
- Division of GastroenterologyDepartment of MedicineDuke UniversityDurham,NC
| | - Keri A. Seymour
- Division of Metabolic SurgeryDepartment of SurgeryDuke UniversityDurhamNC
| | - Ranjan Sudan
- Division of Metabolic SurgeryDepartment of SurgeryDuke UniversityDurhamNC
| | - Dana D. Portenier
- Division of Metabolic SurgeryDepartment of SurgeryDuke UniversityDurhamNC
| | - Anna Mae Diehl
- Division of GastroenterologyDepartment of MedicineDuke UniversityDurham,NC
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Shimada S, Kamiyama T, Orimo T, Nagatsu A, Kamachi H, Taketomi A. High HbA1c is a risk factor for complications after hepatectomy and influences for hepatocellular carcinoma without HBV and HCV infection. Hepatobiliary Surg Nutr 2021; 10:454-463. [PMID: 34430524 DOI: 10.21037/hbsn.2020.01.03] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Accepted: 12/04/2019] [Indexed: 12/11/2022]
Abstract
Background Currently, the population with type 2 diabetes mellitus (DM) is increasing worldwide. However, the influence of DM or hyperglycemia on the outcome of resected hepatocellular carcinoma (HCC) is unclear. Methods We analyzed 756 patients with HCC who underwent hepatectomy. These patients were assigned to an HbA1c ≥7.0% (H-A1c; n=100) or HbA1c <7.0% (L-A1c; n=656) group depending on their HbA1c level at admission. We investigated prognoses, clinicopathological characteristics and surgical outcomes including morbidities of HCC patients with high HbA1c, prognoses according to the treatment for DM were also investigated. Results Among all patients and those with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, overall survival (OS) and relapse-free survival (RFS) did not differ significantly between the H-A1c and L-A1c groups. In contrast, the 5-year OS rate of the H-A1c group was 55% and that of the L-A1c group 71% among patients without HBV and HCV (NBNC patients) (P=0.03). Among NBNC patients, the median RFS of the H-A1c group was 13 months, and that of the L-A1c group was 26 months (P=0.02). In addition, metformin use was an independent favorable factor for both OS and RFS. The H-A1c group had significantly higher rates of hyperbilirubinemia, wound infection, and pneumonia. Conclusions HCC patients with high HbA1c might have poor prognoses for both survival and recurrence in NBNC-HCC. High HbA1c may also be a risk factor for morbidities after hepatectomy. Metformin use may constitute a good option for NBNC patients with HCC.
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Affiliation(s)
- Shingo Shimada
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Toshiya Kamiyama
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Tatsuya Orimo
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Akihisa Nagatsu
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Hirofumi Kamachi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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Lai RM, Chen TB, Hu YH, Wu G, Zheng Q. Effect of type 2 diabetic mellitus in the prognosis of acute-on-chronic liver failure patients in China. World J Gastroenterol 2021; 27:3372-3385. [PMID: 34163118 PMCID: PMC8218358 DOI: 10.3748/wjg.v27.i23.3372] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 04/14/2021] [Accepted: 05/20/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Acute-on-chronic liver failure (ACLF) patients have a high short-term mortality rate, and the severity evaluation of ACLF is necessary for prognostication. Therefore, it was meaningful to evaluate the association between type 2 diabetic mellitus (DM) and ACLF and further explore the feasibility of using DM as a prognostic indicator in ACLF patients. The association between type 2 DM and the prognosis of patients with severe liver disease remains unclear.
AIM To examine the effect of type 2 DM on the prognosis of patients with ACLF.
METHODS Clinical data from 222 ACLF patients were collected and analyzed. The patients were categorized into two groups depending on whether they had DM or not, and the clinical data of ACLF patients were measured within 48 h after admission. Complications of ACLF were documented during treatment, such as hepatic encephalopathy, hepatorenal syndrome, acute upper gastrointestinal hemorrhage, and spontaneous peritonitis (SBP). Values of laboratory parameters, complication rates, and hospital mortality rates were compared between two groups.
RESULTS Among 222 ACLF patients, 38 cases were categorized into DM groups, the mean age was 56.32 years and 73.68% were male. The prognosis of ACLF patients was significantly correlated with DM in univariate [hazard ratio (HR) = 2.4, 95% confidence interval (CI) =1.5-3.7, P < 0.001] and multivariable analysis (HR = 3.17, 95%CI =1.82-5.523, P < 0.001). The incident of SBP (34.21% vs 13.59%, P = 0.038) and other infections like lung, urinary, blood, and cholecyst (44.74% vs 28.26%, P = 0.046) were higher in DM patients than non-DM counterparts. In addition, the ACLF patients with DM tended to have a high mortality rate (P < 0.001). Cumulative survival time was also significantly shorter in the ACLF patients with DM than non-DM.
CONCLUSION A significant association between DM and the prognosis of ACLF patients was found in China. The ACLF patients with DM had higher incidence of hospital mortality and infection than those without DM.
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Affiliation(s)
- Rui-Min Lai
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Tian-Bin Chen
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Yu-Hai Hu
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Gui Wu
- Department of Orthopedics, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Qi Zheng
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
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Shaaban A, Salamah R, Abo Elseud Y, Mohanty A, Albarrak J. Presentation and Outcomes of Hepatocellular Carcinoma in the Arabian Peninsula: A Review of a Single Institution Experience in the Sorafenib Era. J Gastrointest Cancer 2021; 52:85-89. [PMID: 31808059 DOI: 10.1007/s12029-019-00341-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
PURPOSE There is a growing evidence showing that there are geographic differences in hepatocellular carcinoma (HCC). Little is known about the characteristics of hepatocellular carcinoma in the Arabian Peninsula. The present study examines the presentation and outcomes of HCC in a single institution. METHODS A retrospective chart review of patients presented with advanced-stage HCC to Kuwait Cancer Control Center (KCCC) between 2008 and 2018 was conducted. Data collected included patients demographics, HCC risk factors, performance status, Child-Pugh score, pick up of sorafenib, and survival. RESULTS About 111 cases were analyzed. The mean age of the cohort was 61.8 ± 11.4 years and 94 patients (84.7%) were males. HCV and diabetes were the most common risk factors for HCC and presented in 60 patients (54.1%) and 45 patients (40.5%), respectively. About 78 (70.3%) patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 at presentation. Only 29 (26.1%) patients presented with Child-Pugh class A, while 42 (40.4%) patients received sorafenib. The median overall survival was only 3 months. CONCLUSIONS In our cohort, HCV and diabetes were the main risk factors for HCC. The majority of patients was not amenable to sorafenib treatment and carries a very poor prognosis.
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Affiliation(s)
- A Shaaban
- Kuwait Cancer Control Centre, Shuwaikh, Kuwait. .,Minia University Hospital, Menia Governorate, Egypt.
| | - R Salamah
- Kuwait Cancer Control Centre, Shuwaikh, Kuwait
| | | | - A Mohanty
- Kuwait Cancer Control Centre, Shuwaikh, Kuwait
| | - J Albarrak
- Kuwait Cancer Control Centre, Shuwaikh, Kuwait
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Wu HL, Kuo HC, Li CC, Wu YM, Lin SP, Chang KY, Hou MC, Tsou MY, Cherng YG, Chen JT, Tai YH. A comparison of prognostic performance of perioperative inflammation markers in surgical resection for hepatocellular carcinoma. J Chin Med Assoc 2021; 84:614-622. [PMID: 33883464 DOI: 10.1097/jcma.0000000000000534] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Systemic inflammation correlates closely with tumor invasion and may predict survival in cancer patients. We aimed to compare the prognostic value of various inflammation-based markers in patients with hepatocellular carcinoma. METHODS We consecutively enrolled 1450 patients with primary hepatocellular carcinoma undergoing surgical resection at the medical center between 2005 and 2016 and assessed them through September 2018. Prognostic nutritional index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio along with their perioperative dynamic changes were analyzed regarding their predictive ability of postoperative disease-free survival and overall survival. We calculated the adjusted hazard ratio (HR) and 95% CI of the association between inflammation-based markers and survival using multiple Cox proportional hazards models. Youden's index of receiver operating characteristics curves was used to determine optimal cut-off points. RESULTS Prognostic nutritional index was an independent predictor for both disease-free survival (<50.87 vs ≥50.87, HR: 1.274, 95% CI, 1.071-1.517, p = 0.007) and overall survival (<46.65 vs ≥46.65, HR: 1.420, 95% CI, 1.096-1.842, p = 0.008). Besides, the relative change of neutrophil-to-lymphocyte ratio predicted overall survival (<277% vs ≥277%, HR: 1.634, 95% CI, 1.266-2.110, p < 0.001). Combination of both markers offered better prognostic performance for overall survival than either alone. Body mass index, liver cirrhosis, chronic kidney disease, and tumor diameter were significantly associated with both markers. CONCLUSION Prognostic nutritional index and perioperative relative change of neutrophil-to-lymphocyte ratio independently predict postoperative survival in patients undergoing surgical resection of hepatocellular carcinoma. These results provided important evidence for risk stratification and individualized anti-cancer therapy.
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Affiliation(s)
- Hsiang-Ling Wu
- Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Hsien-Cheng Kuo
- Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, ROC
- Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC
| | - Chun-Cheng Li
- Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, ROC
- Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC
| | - Yu-Ming Wu
- Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, ROC
- Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC
| | - Shih-Pin Lin
- Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Kuang-Yi Chang
- Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Ming-Chih Hou
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Mei-Yung Tsou
- Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Yih-Giun Cherng
- Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, ROC
- Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC
| | - Jui-Tai Chen
- Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, ROC
- Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC
| | - Ying-Hsuan Tai
- Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, ROC
- Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC
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Effect of Nonalcoholic Fatty Liver Disease and Metabolic Risk Factors on Waitlist Outcomes in Patients With Hepatocellular Carcinoma. Transplant Direct 2020; 6:e605. [PMID: 33134485 PMCID: PMC7591127 DOI: 10.1097/txd.0000000000001060] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 07/16/2020] [Accepted: 07/17/2020] [Indexed: 12/12/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a leading cause of hepatocellular carcinoma (HCC) in the United States. Prior data suggest that NAFLD-HCC patients are less likely to receive liver transplantation (LT) and have worse overall survival; however, the reason for this discrepancy is unknown.
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Chung W, Promrat K, Wands J. Clinical implications, diagnosis, and management of diabetes in patients with chronic liver diseases. World J Hepatol 2020; 12:533-557. [PMID: 33033564 PMCID: PMC7522556 DOI: 10.4254/wjh.v12.i9.533] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 08/03/2020] [Accepted: 08/15/2020] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus (DM) negatively affects the development and progression of chronic liver diseases (CLD) of various etiologies. Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortality, the occurrence of hepatic decompensation, and the development of hepatocellular carcinoma (HCC). Unfortunately, early diagnosis and optimal treatment of DM can be challenging, due to the lack of established clinical guidelines as well as the medical complexity of this patient population. We conducted an exploratory review of relevant literature to provide an up-to-date review for internists and hepatologists caring for this patient population. We reviewed the epidemiological and pathophysiological associations between DM and CLD, the impact of insulin resistance on the progression and manifestations of CLD, the pathogenesis of hepatogenic diabetes, as well as the practical challenges in diagnosis and monitoring of DM in this patient population. We also reviewed the latest clinical evidence on various pharmacological antihyperglycemic therapies with an emphasis on liver disease-related clinical outcomes. Finally, we proposed an algorithm for managing DM in patients with CLD and discussed the clinical and research questions that remain to be addressed.
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Affiliation(s)
- Waihong Chung
- Division of Gastroenterology, Department of Medicine, Rhode Island Hospital, Providence, RI 02905, United States.
| | - Kittichai Promrat
- Division of Gastroenterology and Hepatology, Providence VA Medical Center, Providence, RI 02908, United States
| | - Jack Wands
- Liver Research Center, The Warren Alpert Medical School of Brown University, Providence, RI 02903, United States
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Fu K, Yang X, Wu H, Gong J, Li X. Diabetes and PKM2 affect prognosis in patients with intrahepatic cholangiocarcinoma. Oncol Lett 2020; 20:265. [PMID: 32989399 PMCID: PMC7517629 DOI: 10.3892/ol.2020.12128] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2020] [Accepted: 08/24/2020] [Indexed: 12/14/2022] Open
Abstract
Diabetes mellitus (DM) is a common disease, but its effect on the prognosis of patients with intrahepatic cholangiocarcinoma (ICC) has not been reported. The aim of the present study was to explore the prognostic significance of diabetes in patients with ICC treated with hepatectomy and to clarify the role of pyruvate kinase M2 (PKM2). A consecutive retrospective cohort of 110 patients with ICC (28 with DM and 82 without DM) who underwent therapeutic hepatectomy was evaluated between January 2006 and January 2011. The clinicopathological characteristics of the two groups and the differences between overall survival (OS) and recurrence-free survival (RFS) were analyzed. The Cox proportional hazards model was further used to identify independent prognostic predictors. PKM2 expression was measured using immunohistochemical staining in tissues collected, after obtaining informed consent. Patients with ICC with DM exhibited significantly lower OS and RFS rates at 1, 3 and 5 years compared with patients with ICC without DM. Cox multivariate analysis revealed that DM was an independent predictor of poor OS and RFS. Additionally, high PKM2 expression was significantly higher in patients with ICC with DM compared with that in patients without DM. Overall, DM was associated with significantly lower OS and RFS rates in patients with ICC. The underlying biological rationale may be attributed to the higher PKM2 expression rate.
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Affiliation(s)
- Kui Fu
- Department of Hepatobiliary Surgery, Traditional Chinese Medicine Hospital of Chongqing Dianjiang, Chongqing 408300, P.R. China
| | - Xiaoli Yang
- Department of Hepatobiliary Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Hao Wu
- Department of Hepatobiliary Surgery, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China
| | - Jianping Gong
- Department of Hepatobiliary Surgery, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China
| | - Xiuyun Li
- Department of Hepatobiliary Surgery, Traditional Chinese Medicine Hospital of Chongqing Dianjiang, Chongqing 408300, P.R. China
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Brar G, Greten TF, Graubard BI, McNeel TS, Petrick JL, McGlynn KA, Altekruse SF. Hepatocellular Carcinoma Survival by Etiology: A SEER-Medicare Database Analysis. Hepatol Commun 2020; 4:1541-1551. [PMID: 33024922 PMCID: PMC7527688 DOI: 10.1002/hep4.1564] [Citation(s) in RCA: 118] [Impact Index Per Article: 23.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Revised: 05/12/2020] [Accepted: 06/18/2020] [Indexed: 12/16/2022] Open
Abstract
In the United States, hepatocellular carcinoma (HCC) survival varies with tumor characteristics, patient comorbidities, and treatment. The effect of HCC etiology on survival is less clearly defined. The relationship between HCC etiology and mortality was examined using Surveillance, Epidemiology, and End Results-Medicare data. In a cohort of 11,522 HCC cases diagnosed from 2000 through 2014, etiologies were identified from Medicare data, including metabolic disorders (32.9%), hepatitis C virus (8.2%), alcohol (4.7%), hepatitis B virus (HBV, 2.1%), rare etiologies (0.9%), multiple etiologies (26.7%), and unknown etiology (24.4%). After adjusting for demographics, tumor characteristics, comorbidities and treatment, hazard ratios (HRs) and survival curves by HCC etiology were estimated using Cox proportional hazard models. Compared with HBV-related HCC cases, higher mortality was observed for those with alcohol-related HCC (HR 1.49; 95% confidence interval [95% CI] 1.25-1.77), metabolic disorder-related HCC (HR 1.25; 95% CI 1.07-1.47), and multiple etiology-related HCC (HR 1.25; 95% CI 1.07-1.46), but was not statistically significant for hepatitis C virus-related, rare disorder-related, and HCC of unknown etiology. For all HCC etiologies, there was short median survival ranging from 6.1 months for alcohol to 10.3 months for HBV. Conclusion: More favorable survival was seen with HBV-related HCC. To the extent that HCC screening is more common among persons with HBV infection compared to those with other etiologic risk factors, population-based HCC screening, applied evenly to persons across all HCC etiology categories, could shift HCC diagnosis to earlier stages, when cases with good clinical status are more amenable to curative therapy.
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Affiliation(s)
- Gagandeep Brar
- Gastrointestinal Malignancy Section Thoracic and Gastrointestinal Malignancies Branch Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD.,Present address: Department of Hematology and Oncology Weill Cornell Medical College New York NY
| | - Tim F Greten
- Gastrointestinal Malignancy Section Thoracic and Gastrointestinal Malignancies Branch Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD
| | - Barry I Graubard
- Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Bethesda MD
| | | | | | - Katherine A McGlynn
- Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Bethesda MD
| | - Sean F Altekruse
- Division of Cardiovascular Science National Heart, Lung and Blood Institute National Institutes of Health Bethesda MD
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Petrelli F, Ghidini M, Rausa E, Ghidini A, Cabiddu M, Borgonovo K, Ghilardi M, Parati MC, Pietrantonio F, Sganzerla P, Bossi AC. Survival of Colorectal Cancer Patients With Diabetes Mellitus: A Meta-Analysis. Can J Diabetes 2020; 45:186-197.e2. [PMID: 33039329 DOI: 10.1016/j.jcjd.2020.06.009] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 06/03/2020] [Accepted: 06/04/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Diabetes mellitus (DM) is associated with an elevated risk of various cancers, including colorectal cancer (CRC). Similarly, pre-existing DM may also influence prognosis among patients with CRC. We performed a systematic review and meta-analysis to assess the association between DM and risk of death and relapse after a diagnosis of CRC. METHODS PubMed, Scopus, Web of Science, The Cochrane Library and Embase were searched from inception until July 2019 for studies reporting prognosis of patients with DM and CRC. The primary outcome of the study refers to overall mortality in patients with vs without diabetes. Secondary endpoints were cancer-specific mortality and progression or relapse-free survival. The risk of death and relapse are reported as hazard ratio (HR) with 95% confidence interval (CI), and an HR >1 was associated with worst outcome in patients with diabetes compared to those without diabetes. RESULTS Mortality and relapse associated with DM in patients with CRC were evaluated among 5,267,980 participants (total of 82 studies). Overall, concomitant diagnosis of CRC and DM were associated with an independent increased risk of overall mortality (HR, 1.21; 95% CI, 1.17 to 1.25; p<0.01) and CSM (HR, 1.11; 95% CI, 1.05 to 1.17; p<0.01). Patients were also at increased risk of relapse (HR, 1.09; 95% CI, 1.02 to 1.16; p<0.01). CONCLUSIONS In CRC patients with DM, diabetes decreased survival and increased the risk of relapse. Adequate control of lifestyle choices, more intensive follow ups, use of some oral antidiabetics, dietary restrictions, physical activity and monitoring of diabetes-associated complications are measures for reducing mortality in this setting.
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Affiliation(s)
- Fausto Petrelli
- Medical Oncology Unit, Azienda Socio-Sanitaria Territoriale Bergamo Ovest, Treviglio, Bergamo, Italy.
| | - Michele Ghidini
- Medical Oncology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy
| | - Emanuele Rausa
- Surgical Oncology Unit, ASST Bergamo Ovest, Treviglio, Bergamo, Italy
| | | | - Mary Cabiddu
- Medical Oncology Unit, Azienda Socio-Sanitaria Territoriale Bergamo Ovest, Treviglio, Bergamo, Italy
| | - Karen Borgonovo
- Medical Oncology Unit, Azienda Socio-Sanitaria Territoriale Bergamo Ovest, Treviglio, Bergamo, Italy
| | - Mara Ghilardi
- Medical Oncology Unit, Azienda Socio-Sanitaria Territoriale Bergamo Ovest, Treviglio, Bergamo, Italy
| | - Maria Chiara Parati
- Medical Oncology Unit, Azienda Socio-Sanitaria Territoriale Bergamo Ovest, Treviglio, Bergamo, Italy
| | - Filippo Pietrantonio
- Oncology Unit, Fondazione IRCCS, Istituto Nazionale Tumori di Milano, Milano, Italia
| | - Paolo Sganzerla
- Cardiology Unit, ASST Bergamo Ovest, Treviglio, Bergamo, Italy
| | - Antonio Carlo Bossi
- Endocrine Diseases Unit‒Diabetes Regional Center, ASST Bergamo Ovest, Treviglio, Bergamo, Italy
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Wang M, Yang Y, Liao Z. Diabetes and cancer: Epidemiological and biological links. World J Diabetes 2020; 11:227-238. [PMID: 32547697 PMCID: PMC7284016 DOI: 10.4239/wjd.v11.i6.227] [Citation(s) in RCA: 87] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Revised: 04/24/2020] [Accepted: 05/05/2020] [Indexed: 02/06/2023] Open
Abstract
The incidence of diabetes and cancer has increased significantly in recent years. Furthermore, there are many common risk factors for both diabetes and cancer, such as obesity, sedentary lifestyle, smoking, and ageing. A large body of epidemiological evidence has indicated that diabetes is considered as an independent risk factor for increased rates of heterogeneous types of cancer occurrence and death. The incidence and mortality of various types of cancer, such as pancreas, liver, colorectal, breast, endometrial, and bladder cancers, have a modest growth in diabetics. However, diabetes may work as a protective factor for prostate cancer. Although the underlying biological mechanisms have not been totally understood, studies have validated that insulin/insulin-like growth factor (IGF) axis (including insulin resistance, hyperinsulinemia, and IGF), hyperglycemia, inflammatory cytokines, and sex hormones provide good circumstances for cancer cell proliferation and metastasis. Insulin/IGF axis activates several metabolic and mitogenic signaling pathways; hyperglycemia provides energy for cancer cell growth; inflammatory cytokines influence cancer cell apoptosis. Thus, these three factors affect all types of cancer, while sex hormones only play important roles in breast cancer, endometrial cancer, and prostate cancer. This minireview consolidates and discusses the epidemiological and biological links between diabetes and various types of cancer.
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Affiliation(s)
- Mina Wang
- School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore
- The Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing 100010, China
- Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Yingying Yang
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna 17177, Sweden
- Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Zehuan Liao
- School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore
- Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Solna 17177, Sweden
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Plaz Torres MC, Bodini G, Furnari M, Marabotto E, Zentilin P, Strazzabosco M, Giannini EG. Surveillance for Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease: Universal or Selective? Cancers (Basel) 2020; 12:E1422. [PMID: 32486355 PMCID: PMC7352281 DOI: 10.3390/cancers12061422] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 05/22/2020] [Accepted: 05/24/2020] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC), the most frequent primary liver cancer, is the sixth most common cancer, the fourth leading cause of cancer-related deaths worldwide, and accounts globally for about 800,000 deaths/year. Early detection of HCC is of pivotal importance as it is associated with improved survival and the ability to apply curative treatments. Chronic liver diseases, and in particular cirrhosis, are the main risk factors for HCC, but the etiology of liver disease is rapidly changing due to improvements in the prevention and treatment of HBV (Hepatitis B virus) and HCV (Hepatitis C virus) infections and to the rising incidence of the metabolic syndrome, of which non-alcoholic fatty liver (NAFLD) is a manifestation. NAFLD is now a recognized and rapidly increasing cause of cirrhosis and HCC. Indeed, the most recent guidelines for NAFLD management recommend screening for HCC in patients with established cirrhosis. Screening in NAFLD patients without cirrhosis is not recommended; however, the prevalence of HCC in this group of NAFLD patients has been reported to be as high as 38%, a proportion significantly higher than the one observed in the general population and in non-cirrhotic subjects with other causes of liver disease. Unfortunately, solid data regarding the risk stratification of patients with non-cirrhotic NAFLD who might best benefit from HCC surveillance are scarce, and specific recommendations in this field are urgently needed due to the increasing NAFLD epidemic, at least in Western countries. To further complicate matters, liver ultrasonography, which represents the current standard for HCC surveillance, has a decreased diagnostic accuracy in patients with NAFLD, and therefore disease-specific surveillance tools will be required for the early identification of HCC in this population. In this review, we summarize the most recent evidence on the epidemiology and risk factors for HCC in patients with NAFLD, with and without cirrhosis, and the evidence supporting surveillance for early HCC detection in these patients, reviewing the potential limitations of currently recommended surveillance strategies, and assessing data on the accuracy of potential new screening tools. At this stage it is difficult to propose general recommendations, and best clinical judgement should be exercised, based on the profile of risk factors specific to each patient.
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Affiliation(s)
- Maria Corina Plaz Torres
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS-Ospedale Policlinico San Martino, 16132 Genoa, Italy; (M.C.P.T.); (G.B.); (M.F.); (E.M.); (P.Z.)
| | - Giorgia Bodini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS-Ospedale Policlinico San Martino, 16132 Genoa, Italy; (M.C.P.T.); (G.B.); (M.F.); (E.M.); (P.Z.)
| | - Manuele Furnari
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS-Ospedale Policlinico San Martino, 16132 Genoa, Italy; (M.C.P.T.); (G.B.); (M.F.); (E.M.); (P.Z.)
| | - Elisa Marabotto
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS-Ospedale Policlinico San Martino, 16132 Genoa, Italy; (M.C.P.T.); (G.B.); (M.F.); (E.M.); (P.Z.)
| | - Patrizia Zentilin
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS-Ospedale Policlinico San Martino, 16132 Genoa, Italy; (M.C.P.T.); (G.B.); (M.F.); (E.M.); (P.Z.)
| | - Mario Strazzabosco
- Liver Center and Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA;
| | - Edoardo G. Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS-Ospedale Policlinico San Martino, 16132 Genoa, Italy; (M.C.P.T.); (G.B.); (M.F.); (E.M.); (P.Z.)
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Zhou J, Ke Y, Lei X, Wu T, Li Y, Bao T, Tang H, Zhang C, Wu X, Wang G, Li J, Zhang H, Ni F, Ye Z, Wang L. Meta-analysis: The efficacy of metformin and other anti-hyperglycemic agents in prolonging the survival of hepatocellular carcinoma patients with type 2 diabetes. Ann Hepatol 2020; 19:320-328. [PMID: 31980358 DOI: 10.1016/j.aohep.2019.11.008] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Revised: 10/30/2019] [Accepted: 11/14/2019] [Indexed: 02/04/2023]
Abstract
INTRODUCTION This study aimed to compare the therapeutic efficacy of metformin and other anti-hyperglycemic agents in hepatocellular carcinoma (HCC) patients with type 2 diabetes (T2D). MATERIALS A systematic electronic search on keywords including HCC and different anti-hyperglycemic agents was performed through electronic databases including Medline and EMBASE. The primary outcome was the overall survival (OS). The secondary outcomes were the recurrence-free survival (RFS) and progression-free survival (PFS). RESULTS Six retrospective cohort studies were included for analysis: Four studies with curative treatment for HCC (618 patients with metformin and 532 patients with other anti-hyperglycemic agents) and two studies with non-curative treatment for HCC (92 patients with metformin and 57 patients with other anti-hyperglycemic agents). Treatment with metformin was associated with significantly longer OS (OR1yr=2.62, 95%CI: 1.76-3.90; OR3yr=3.14, 95%CI: 2.33-4.24; OR5yr=3.31, 95%CI: 2.39-4.59, all P<0.00001) and RFS (OR1yr=2.52, 95%CI: 1.84-3.44; OR3yr=2.87, 95%CI: 2.15-3.84; all P<0.00001; and OR5yr=2.26, 95%CI: 0.94-5.45, P=0.07) rates vs. those of other anti-hyperglycemic agents after curative therapies for HCC. However, both of the two studies reported that following non-curative HCC treatment, there were no significant differences in the OS and PFS rates between the metformin and non-metformin groups (I2>50%). CONCLUSIONS Metformin significantly prolonged the survival of HCC patients with T2D after the curative treatment of HCC. However, the efficacy of metformin needs to be further determined after non-curative therapies for HCC patients with T2D.
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Affiliation(s)
- Jian Zhou
- Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China; The Yunnan Provincial Clinical Center for Hepato-biliary-pancreatic Diseases, Kunming, Yunnan, China
| | - Yang Ke
- Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China; The Yunnan Provincial Clinical Center for Hepato-biliary-pancreatic Diseases, Kunming, Yunnan, China
| | - Xuefen Lei
- Department of Medical Oncology, the Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Tiangen Wu
- Department of Gastroenterological Surgery, the Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Yuehua Li
- Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China; The Yunnan Provincial Clinical Center for Hepato-biliary-pancreatic Diseases, Kunming, Yunnan, China
| | - Tianhao Bao
- Mental Health Center of Kunming Medical University, Kunming, Yunnan, China
| | - Haoran Tang
- Department of Gastroenterological Surgery, the Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Cheng Zhang
- Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China; The Yunnan Provincial Clinical Center for Hepato-biliary-pancreatic Diseases, Kunming, Yunnan, China; Department of Hepatobiliary Surgery, the Sixth People's Hospital of Chengdu, Chengdu, Sichuan, China
| | - Xuesong Wu
- Department of Gastroenterological Surgery, the Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Ge Wang
- Department of Gastroenterological Surgery, the Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Jinze Li
- Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China; The Yunnan Provincial Clinical Center for Hepato-biliary-pancreatic Diseases, Kunming, Yunnan, China
| | - Heng Zhang
- Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China; The Yunnan Provincial Clinical Center for Hepato-biliary-pancreatic Diseases, Kunming, Yunnan, China
| | - Fan Ni
- Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China; The Yunnan Provincial Clinical Center for Hepato-biliary-pancreatic Diseases, Kunming, Yunnan, China
| | - Zhengchen Ye
- Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China; The Yunnan Provincial Clinical Center for Hepato-biliary-pancreatic Diseases, Kunming, Yunnan, China
| | - Lin Wang
- Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China; The Yunnan Provincial Clinical Center for Hepato-biliary-pancreatic Diseases, Kunming, Yunnan, China.
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Antwi SOP, Li Z, Mody K, Roberts LR, Patel T. Independent and Joint Use of Statins and Metformin by Elderly Patients With Diabetes and Overall Survival Following HCC Diagnosis. J Clin Gastroenterol 2020; 54:468-476. [PMID: 32271517 PMCID: PMC7150664 DOI: 10.1097/mcg.0000000000001182] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
GOAL To investigate associations of prediagnosis and postdiagnosis use of statins and metformin on overall survival of patients with diabetes who later developed HCC. BACKGROUND Statins and metformin have received considerable interest as potential chemopreventive agents against hepatocellular carcinoma (HCC) development in individuals with type 2 diabetes mellitus (T2DM); however, their impact on overall survival of patients with T2DM who later develop HCC (diabetic HCC patients) is unclear. STUDY Data on 2499 elderly diabetic HCC patients obtained from the SEER-Medicare program (2009 to 2013) were analyzed. Patients were categorized based on use of statins only, metformin only, both, or neither (reference for all comparisons). The patients were further categorized based on: (1) metformin dose: ≤1500 or >1500 mg/d; (2) statins functional form: hydrophilic (pravastatin and rosuvastatin) or lipophilic (atorvastatin, fluvastatin, lovastatin, and simvastatin); (3) statins potency: high (atorvastatin, rosuvastatin, and simvastatin) or low (fluvastatin, lovastatin, and pravastatin); and (4) individual statins type. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard models. RESULTS Prediagnosis use of metformin dose ≤1500 mg/d was associated with lower risk of death after HCC diagnosis in patients with T2DM (HR, 0.72; 95% CI, 0.58-0.91), adjusting for postdiagnosis metformin dose, diabetes severity, Charlson comorbidity index, tumor characteristics, and other relevant factors. No association was found for prediagnosis metformin dose >1500 mg/d or postdiagnosis metformin use. Further, no association was found for either prediagnosis or postdiagnosis statins use. CONCLUSIONS Prediagnosis use of metformin dose ≤1500 mg/d is associated with longer overall survival of elderly diabetic HCC patients.
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Affiliation(s)
| | - Zhuo Li
- Health Sciences Research, Mayo Clinic, Jacksonville, FL
| | - Kabir Mody
- Medical Oncology, Mayo Clinic, Jacksonville, FL
| | | | - Tushar Patel
- Transplant Hepatology, Mayo Clinic, Jacksonville, FL
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Leone S, Lorenzini P, Cozzi-Lepri A, Orofino G, Bernacchia D, Castagna A, Menozzi M, Guaraldi G, Madeddu G, Di Biagio A, Puoti M, Gori A, d'Arminio Monforte A. Impact of diabetes on the risk of serious liver events and liver-related deaths in people living with HIV and hepatitis C co-infection: data from the ICONA Foundation Cohort Study. Eur J Clin Microbiol Infect Dis 2019; 38:1857-1865. [PMID: 31230205 DOI: 10.1007/s10096-019-03618-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Accepted: 06/14/2019] [Indexed: 12/29/2022]
Abstract
To investigate the association between diabetes and HCV infection in persons living with HIV and to determine the impact of diabetes on the occurrence of serious liver events (SLEs) and liver-related deaths (LRDs) among HIV/HCV-co-infected patients. Patients were included if they had at least one follow-up visit. In a cross-sectional analysis among all HIV patients, we have investigated the association between diabetes and HCV infection. A further longitudinal analysis was performed in the population of HIV/HCV-co-infected free from SLE with FIB-4 index < 3.25 at baseline, using the following endpoints: (A) first event between SLE and LRD; (B) liver fibrosis progression defined as the first of two consecutive FIB-4 > 3.25; (C) first event between SLE, LRD, and liver fibrosis progression. Data from 15,571 HIV patients were analyzed: 2944 (18.9%) were HCV-Ab positive, and 739 (4.7%) presented a diagnosis of diabetes at their last follow-up. Among HIV/HCV-co-infected population, 107 patients had a diagnosis of diabetes. Viremic HCV-co-infected patients had 3-fold risk of diabetes onset than HCV-uninfected patients. On HIV/HCV-co-infected population, 85 SLEs/LRDs occurred over 20,410 person-years of follow-up (PYFU), for an incidence rate of 4.2/1000 PYFU (95%CI 3.4-5.2). Diabetic patients had 3-fold risk of pooled SLE and LRD than patients without diabetes. Furthermore, viremic HCV infection was independently associated with a higher risk of SLE/LRD (aIRR 3.35 [95%CI 1.14-9.83]). In HIV-infected patients, viremic HCV co-infection is a strong predictor of diabetes. Among HIV/HCV-co-infected population, diabetic patients showed an increased risk of SLE/LRD compared with those without diabetes.
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Affiliation(s)
- Sebastiano Leone
- Division of Infectious Diseases, Department of Internal Medicine, San Giuseppe Moscati Hospital, Contrada Amoretta, 83100, Avellino, Italy.
| | | | | | | | - Dario Bernacchia
- Infectious Diseases Unit, ASST Fatebenefratelli-Sacco, DIBIC 'L. Sacco', University of Milan, Milan, Italy
| | - Antonella Castagna
- Infectious Diseases Department, IRCCS San Raffaele Scientific Institute & Vita-Salute University, Milan, Italy
| | - Marianna Menozzi
- Clinic of Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy
| | - Giovanni Guaraldi
- Clinic of Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy
| | - Giordano Madeddu
- Infectious Diseases Unit, Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy
| | - Antonio Di Biagio
- Infectious Diseases Unit, Policlinico San Martino Hospital, Genoa, Italy
| | - Massimo Puoti
- Infectious Diseases Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Andrea Gori
- Infectious Diseases Unit, Department of Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.,Department of Pathophysiology and Transplantation, School of Medicine and Surgery, University of Milan, Milan, Italy
| | - Antonella d'Arminio Monforte
- Clinic of Infectious and Tropical Diseases, Department of Health Sciences, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy
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Chronic Viral Hepatitis Signifies the Association of Premixed Insulin Analogues with Liver Cancer Risks: A Nationwide Population-Based Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16122097. [PMID: 31200528 PMCID: PMC6616640 DOI: 10.3390/ijerph16122097] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Revised: 06/09/2019] [Accepted: 06/12/2019] [Indexed: 02/07/2023]
Abstract
This study sought to determine whether chronic hepatitis B or C would modify the association between insulin analogues and hepatocellular carcinoma (HCC) risks. We conducted a nationwide nested case-control study for HCC cases and matched controls from 2003 to 2013 among newly diagnosed type 2 diabetes patients on any antidiabetic agents in Taiwan before and after exclusion of chronic viral hepatitis, respectively. A total of 5832 and 1237 HCC cases were identified before and after exclusion of chronic viral hepatitis, respectively. Incident HCC risks were positively associated with any use of premixed insulin analogues (adjusted odds ratio (OR), 1.27; 95% CI 1.04 to 1.55) among total participants, especially among current users (adjusted OR, 1.45; 95% CI 1.12 to 1.89). However, the association between HCC occurrence and premixed insulin analogues diminished among participants without chronic viral hepatitis (adjusted OR, 1.35; 95% CI 0.92 to 1.98). We also observed a significant multiplicative interaction between chronic viral hepatitis and premixed insulin analogues on HCC risks (P = 0.010). Conclusions: Chronic viral hepatitis signifies the role of premixed insulin analogues in HCC oncogenesis. We recommend a closer liver surveillance among patients prescribed premixed insulin analogues with concomitant chronic viral hepatitis.
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Kim TH, Chang JM, Um SH, Jee H, Lee YR, Lee HA, Yim SY, Han NY, Lee JM, Choi HS, Kim ES, Yu YD, Keum B, Kim MJ, An H, Park BJ, Seo YS, Kim DS, Yim HJ, Cho SB, Jeen YT, Lee HS, Chun HJ, Kim YH, Kim CD. Comparison of 2 curative treatment options for very early hepatocellular carcinoma: Efficacy, recurrence pattern, and retreatment. Medicine (Baltimore) 2019; 98:e16279. [PMID: 31261600 PMCID: PMC6616374 DOI: 10.1097/md.0000000000016279] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Curative treatments for very early-stage hepatocellular carcinoma (HCC), defined as single HCC with a maximum diameter of <2 cm in patients with well-preserved liver function, consist of surgical resection or radiofrequency ablation (RFA). In this retrospective study, we compared the efficacy of both treatments in 154 patients with very early-stage HCCs who underwent resection or RFA as initial therapy and were followed up for a median of 56.8 months. Propensity score matching analysis was also conducted. Overall survival was comparable between treatment groups (median survival time of 143 vs 97 months for resection and RFA, respectively; P = .132). Resection group; however, demonstrated a significantly lower recurrence rate after initial therapy than RFA group (42.3% vs 65.7%; P = .006) with a longer median recurrence-free survival time (66.7 vs 33.8 months; P = .002), which was confirmed even after matching (P = .04). In contrast, the recurrence pattern in advanced-stage (9.6% vs 1.0%; P = .01) or incurable recurrences (19% vs 13%; P = .04) was more frequent following resection than RFA. Recurrent lesions were comparatively more curable in RFA group than in resection group (80% vs 54.5%; P = .02). The recurrence of HCC was independently associated with lower serum albumin level (P = .027), the presence of comorbid diabetes mellitus (P = .010), and RFA (P = .034). In conclusion, in patients with very early-stage HCC, surgical resection has achieved significantly better recurrence-free survival than RFA. A closer follow-up is required after resection.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Young-Dong Yu
- Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | | | | | | | | | | | - Dong-Sik Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Korea
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Yin JB, Niu Y, Qian LY, Zhang X, Liu ZP, Wang RT. Mean platelet volume predicts survival in patients with hepatocellular carcinoma and type 2 diabetes. Diabetes Res Clin Pract 2019; 151:120-127. [PMID: 30959147 DOI: 10.1016/j.diabres.2019.04.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2018] [Revised: 03/14/2019] [Accepted: 04/01/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Patients with hepatocellular carcinoma (HCC) having pre-existing type 2 diabetes (T2DM) have a poorer prognosis than those without T2DM. Moreover, accumulating evidence reveals that activated platelets play a crucial role in tumor and T2DM. The mean platelet volume (MPV) indicates platelet activation and is altered in malignancies. The present study aimed to investigate the clinical significance of MPV in patients with HCC having T2DM. METHODS This retrospective study performed between January 2010 and December 2013 included 331 patients with HCC (165 with T2DM and 166 without T2DM). The overall survival was compared, and the predictors of overall survival were analyzed. RESULTS The patients with T2DM had lower MPV levels than those without T2DM. Furthermore, the MPV levels significantly differentiated T2DM from non-T2DM. In addition, for patients with T2DM, the overall survival was significantly shorter in patients with low MPV levels than in those with high MPV levels. Multivariate analysis identified decreased MPV as an independent prognostic factor for overall survival only in patients with T2DM, but not in those without T2DM. CONCLUSION Reduced MPV was a prognostic factor for poor outcome in patients with HCC and T2DM.
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Affiliation(s)
- Ji-Bin Yin
- Department of Gastroenterology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150086, China
| | - Ye Niu
- Department of Geriatrics, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150086, China
| | - Li-Yan Qian
- Changsheng Township Health Center, Jiayin County, Yichun city, Heilongjiang 153215, China
| | - Xin Zhang
- Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, China
| | - Zhi-Ping Liu
- Departments of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Rui-Tao Wang
- Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, China.
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Ren H, Wang J, Gao Y, Yang F, Huang W. Metabolic syndrome and liver-related events: a systematic review and meta-analysis. BMC Endocr Disord 2019; 19:40. [PMID: 31023282 PMCID: PMC6485158 DOI: 10.1186/s12902-019-0366-3] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2019] [Accepted: 04/08/2019] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Previous studies have suggested that metabolic syndrome (MetS) and its component conditions are linked to the development of many benign or malignant diseases. Some studies have described relationships among metabolic syndrome or diabetes and liver cancer, but not many articles described the relationships between MetS and cirrhosis, acute hepatic failure, end-stage liver disease, and even death. However, liver cancers, cirrhosis, acute hepatic failure, end-stage liver disease, and liver-related mortality-collectively described as liver-related events (LREs)-may have different relationships with MetS. We undertook this meta-analysis to examine the association between MetS and LREs, and to determine whether geographic region or hepatitis B virus (HBV) positivity might influence the association. METHODS Relevant studies were identified from PubMed, EMBASE, and the Cochrane database. Two reviewers independently searched records from January 1980 to December 2017. The search terms included 'metabolic syndrome', 'diabetes mellitus', 'insulin resistance syndrome', and 'metabolic abnormalities', combined with 'cirrhosis', 'hepatic fibrosis ', 'hepatocellular carcinoma', 'complication', 'LRE', 'HCC', 'liver-related events', and 'liver cancer'. No language restriction was applied to the search. We chose the studies reporting an association between MetS and LREs. We used Begg's and Egger's tests and visually examined a funnel plot to assess publication bias. All analyses were conducted in Stata 14.0 software. RESULTS There were 19 studies (18 cohort and 1 case-control) included in the analysis, with a total of 1,561,457 participants. The subjects' ages ranged from 18 to 84 years. The combined analysis showed an overall 86% increase risk of LREs in cases with MetS (RR: 1.86,95% CI: 1.56-2.23). The funnel plot was asymmetrical, and the Egger's test p values showed a publication bias in this meta analysis. However, through the trim and fill method, we obtained a new RR value for LREs with MetS of 1.49 (95% CI: 1.40-1.58, p = 0.000). There was no obvious difference with the two answers, so we concluded that the results were robust. For hepatitis B positive patients, the RR for MetS and LREs was 2.15 (95% CI:1.02-4.53, p = 0.038), but for the hepatitis B negative patients, the RR was 1.85 (95% CI:1.53-2.24, p = 0.000). And for non-Asians, the RR for MetS and LREs was 2.21 (95% CI: 1.66-2.69, p = 0.000), while for Asians, the RR was 1.73 (95% CI: 1.35-2.22, p = 0.000). CONCLUSIONS This meta-analysis showed that MetS is associated with a moderately increased risk of LREs prevalence. Patients with MetS together with hepatitis B are more likely to develop hepatic events. For non-Asians, MetS is more likely to increase the incidence of LREs.
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Affiliation(s)
- Huina Ren
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016 China
| | - Junna Wang
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016 China
| | - Yue Gao
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016 China
| | - Fuwei Yang
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016 China
| | - Wenxiang Huang
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016 China
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