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1
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Moon AM. Raising the Bar: Is Hepatocellular Carcinoma Surveillance Warranted for Patients With Alcohol-Associated Cirrhosis? Am J Gastroenterol 2025; 120:540-541. [PMID: 39445687 DOI: 10.14309/ajg.0000000000003123] [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: 09/19/2024] [Accepted: 09/24/2024] [Indexed: 10/25/2024]
Affiliation(s)
- Andrew M Moon
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina, USA
- Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA
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2
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Ganne-Carrié N, Nahon P. Differences between hepatocellular carcinoma caused by alcohol and other aetiologies. J Hepatol 2024:S0168-8278(24)02817-4. [PMID: 39710147 DOI: 10.1016/j.jhep.2024.12.030] [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: 08/28/2024] [Revised: 11/14/2024] [Accepted: 12/07/2024] [Indexed: 12/24/2024]
Abstract
Alcohol-related liver disease is the third cause of hepatocellular carcinoma worldwide and the leading cause in Europe. Additionally, the recent definition of Metabolic dysfunction-Associated Steatotic Liver Disease with increased alcoholic intake will enrich this population with a more nuanced phenotype, reflecting recent epidemiological trends. In these patients, hepatocellular carcinoma diagnosis is often delayed and less frequently detected through screening programs. Moreover, at the time of diagnosis, patients with alcohol-related hepatocellular carcinoma tend to have a poorer general condition, more severely impaired liver function, and a higher prevalence of comorbidities, leading to increased competitive mortality. However, when hepatocellular carcinoma is diagnosed during surveillance programs in patients with alcohol-related liver disease or metabolic dysfunction-Associated steatotic liver disease with increased alcoholic intake, the rate of allocation to first-line curative treatments is high (56%) and comparable to that of patients with virus-related hepatocellular carcinoma. As a consequence, the etiology of the underlying cirrhosis cannot be considered an independent prognostic factor in patients with hepatocellular carcinoma. Instead, prognosis is driven by liver function, general condition, and tumor burden. This underscores the crucial role of early diagnosis through periodic surveillance in patients with Alcohol-related liver disease or Metabolic dysfunction-Associated Steatotic Liver Disease with increased alcoholic intake -related cirrhosis.
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Affiliation(s)
- Nathalie Ganne-Carrié
- AP-HP, Hôpital Avicenne, Liver Unit, F-93000 Bobigny, France; University Sorbonne Paris Nord, UFR SMBH, F-93000 Bobigny, France; INSERM UMR-1168, Functional Genomics of Solid Tumours, F-75006 Paris, France.
| | - Pierre Nahon
- AP-HP, Hôpital Avicenne, Liver Unit, F-93000 Bobigny, France; University Sorbonne Paris Nord, UFR SMBH, F-93000 Bobigny, France; INSERM UMR-1168, Functional Genomics of Solid Tumours, F-75006 Paris, France
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3
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Fu Y, Maccioni L, Wang XW, Greten TF, Gao B. Alcohol-associated liver cancer. Hepatology 2024; 80:1462-1479. [PMID: 38607725 DOI: 10.1097/hep.0000000000000890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 03/28/2024] [Indexed: 04/14/2024]
Abstract
Heavy alcohol intake induces a wide spectrum of liver diseases ranging from steatosis, steatohepatitis, cirrhosis, and HCC. Although alcohol consumption is a well-known risk factor for the development, morbidity, and mortality of HCC globally, alcohol-associated hepatocellular carcinoma (A-HCC) is poorly characterized compared to viral hepatitis-associated HCC. Most A-HCCs develop after alcohol-associated cirrhosis (AC), but the direct carcinogenesis from ethanol and its metabolites to A-HCC remains obscure. The differences between A-HCC and HCCs caused by other etiologies have not been well investigated in terms of clinical prognosis, genetic or epigenetic landscape, molecular mechanisms, and heterogeneity. Moreover, there is a huge gap between basic research and clinical practice due to the lack of preclinical models of A-HCC. In the current review, we discuss the pathogenesis, heterogeneity, preclinical approaches, epigenetic, and genetic profiles of A-HCC, and discuss the current insights into and the prospects for future research on A-HCC. The potential effect of alcohol on cholangiocarcinoma and liver metastasis is also discussed.
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Affiliation(s)
- Yaojie Fu
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
| | - Luca Maccioni
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
| | - Xin Wei Wang
- Liver Carcinogenesis Section, Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland, USA
- Liver Cancer Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA
| | - Tim F Greten
- Liver Cancer Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA
- Gastrointestinal Malignancies Section, Thoracic and Gastrointestinal Malignancies Branch, National Cancer Institute, NIH, Bethesda, Maryland, USA
| | - Bin Gao
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
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4
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Zeng RW, Ong CEY, Ong EYH, Chung CH, Lim WH, Xiao J, Danpanichkul P, Law JH, Syn N, Chee D, Kow AWC, Lee SW, Takahashi H, Kawaguchi T, Tamaki N, Dan YY, Nakajima A, Wijarnpreecha K, Muthiah MD, Noureddin M, Loomba R, Ioannou GN, Tan DJH, Ng CH, Huang DQ. Global Prevalence, Clinical Characteristics, Surveillance, Treatment Allocation, and Outcomes of Alcohol-Associated Hepatocellular Carcinoma. Clin Gastroenterol Hepatol 2024; 22:2394-2402.e15. [PMID: 38987014 DOI: 10.1016/j.cgh.2024.06.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 05/25/2024] [Accepted: 06/02/2024] [Indexed: 07/12/2024]
Abstract
BACKGROUND Although the burden of alcohol-associated hepatocellular carcinoma (HCC) is increasing with rising alcohol consumption, clinical presentation and outcomes of alcohol-associated HCC have not been systematically assessed. We aimed to determine the prevalence, clinical characteristics, surveillance rates, treatment allocation, and outcomes of alcohol-associated HCC. METHODS Medline and Embase were searched from inception to January 2023. Proportional data were analyzed using a generalized linear mixed model. The odds ratio (OR) or mean difference comparing alcohol-associated HCC and other causes was obtained with pairwise meta-analysis. Survival outcomes were evaluated using a pooled analysis of hazard ratios. RESULTS Of 4824 records identified, 55 articles (86,345 patients) were included. Overall, 30.4% (95% confidence interval [CI], 24.0%-37.7%) of HCC was alcohol associated, with the highest proportion in Europe and the lowest in the Americas. People with alcohol-associated HCC were more likely male but were similar in age and comorbidities compared with other causes. A total of 20.8% (95% CI, 11.4%-34.9%) of people with alcohol-associated HCC underwent surveillance compared with 35.0%, 31.6%, and 21.4% in hepatitis B virus, hepatitis C virus, and metabolic dysfunction-associated HCC, respectively (all P < .05). Alcohol-associated HCC had a lower likelihood of Barcelona Clínic Liver Cancer C stage (0/A) (OR, 0.7; 95% CI, 0.6-0.9; P = .018) and curative therapy (24.5% vs 33.9%; OR, 0.7; 95% CI, 0.5-0.9; P = .003), and higher mortality (HR, 1.3; 95% CI, 1.1-1.5; P = .012) when compared with other causes. CONCLUSIONS Alcohol-associated HCC is associated with lower surveillance rates, more advanced BCLC stage, lower likelihood of receiving curative therapy, and poorer survival. These data call for measures to reduce heavy alcohol consumption and improve strategies for effective HCC surveillance in high-risk individuals.
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Affiliation(s)
| | - Christen En Ya Ong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Elden Yen Hng Ong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Charlotte Hui Chung
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jieling Xiao
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | | | - Jia Hao Law
- Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, National University Hospital, Singapore
| | - Nicholas Syn
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Biostatistics & Modelling Domain, Saw Swee Hock School of Public Health, National University of Singapore, Singapore
| | - Douglas Chee
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore
| | - Alfred Wei Chieh Kow
- Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, National University Hospital, Singapore; Division of Surgical Oncology, National University Cancer Institute, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Sung Won Lee
- Division of Hepatology, Department of Internal Medicine, Catholic University of Korea, Seoul, Republic of Korea
| | | | - Takumi Kawaguchi
- Department of Digestive Disease Information & Research, School of Medicine, Kurume University, Fukuoka, Japan
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yock Young Dan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Atsushi Nakajima
- Graduate School of Medicine, Yokohama City University, Yokohama, Japan
| | - Karn Wijarnpreecha
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Arizona College of Medicine, Phoenix, Arizona; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Banner University Medical Center, Phoenix, Arizona
| | - Mark D Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | | | - Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California
| | - George N Ioannou
- Division of Gastroenterology, Department of Medicine, Veterans Affairs Puget Sound Health Care System, Seattle, Washington; Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, Washington
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Digestive Disease Information & Research, School of Medicine, Kurume University, Fukuoka, Japan
| | - Daniel Q Huang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore.
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5
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Ha NB, Yao F. Alcohol and Hepatocellular Carcinoma. Clin Liver Dis 2024; 28:633-646. [PMID: 39362712 DOI: 10.1016/j.cld.2024.06.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/05/2024]
Abstract
Alcohol-associated liver disease (ALD) poses a significant risk for hepatocellular carcinoma (HCC), comprising various liver conditions from steatosis to cirrhosis. Despite accounting for a third of global HCC cases and deaths, ALD-related HCC lacks characterization compared to viral hepatitis-related HCC. Proposed mechanisms for ALD-related HCC include acetaldehyde toxicity, increased reactive oxygen species, and inflammation. This review examines ALD-associated HCC epidemiology, co-factors like viral hepatitis and metabolic syndrome, surveillance, and treatment challenges. Despite advances in screening and management, ALD-related HCC often presents at advanced stages, limiting treatment options and survival.
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Affiliation(s)
- Nghiem B Ha
- Hepatology, Liver Transplant, Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, 505 Parnassus Avenue, S-357, San Francisco, CA 94112, USA
| | - Francis Yao
- Hepatology, Liver Transplant, Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, 505 Parnassus Avenue, S-357, San Francisco, CA 94112, USA.
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6
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Feng X, Huang N, Wu Y, Gao F, Chen X, Zhang C, Zhang B, Sun T. Alcoholic Liver Disease in China: A Disease Influenced by Complex Social Factors That Should Not Be Neglected. J Clin Transl Hepatol 2024; 12:677-684. [PMID: 38993514 PMCID: PMC11233974 DOI: 10.14218/jcth.2024.00034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 04/26/2024] [Accepted: 05/06/2024] [Indexed: 07/13/2024] Open
Abstract
Alcoholic liver disease (ALD) encompasses liver damage caused by chronic, excessive alcohol consumption. It manifests initially as marked hepatocellular steatosis and can progress to steatohepatitis, liver fibrosis, and cirrhosis. With China's rapid economic growth, coupled with a complex social background and the influence of a deleterious wine culture, the number of patients with ALD in China has increased significantly; the disease has become a social and health problem that cannot be ignored. In this review, we briefly described the social factors affecting ALD in China and elaborated on differences between alcoholic and other liver diseases in terms of complications (e.g., cirrhosis, upper gastrointestinal bleeding, hepatic encephalopathy, hepatocellular carcinoma, addiction, and other extrahepatic diseases). We also emphasized that ALD was more dangerous and difficult to treat than other liver diseases due to its complications, and that precise and effective treatment measures were lacking. In addition, we considered new ideas and treatment methods that may be generated in the future.
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Affiliation(s)
- Xiaofeng Feng
- The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Nafei Huang
- The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Yuqin Wu
- The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Fei Gao
- The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Xiaomei Chen
- The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Chenyi Zhang
- The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Bing Zhang
- Hangzhou First People's Hospital, Hangzhou, Zhejiang, China
| | - Tao Sun
- The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
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7
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Kim HY, Lee HA, Radu P, Dufour JF. Association of modifiable metabolic risk factors and lifestyle with all-cause mortality in patients with hepatocellular carcinoma. Sci Rep 2024; 14:15405. [PMID: 38965260 PMCID: PMC11224327 DOI: 10.1038/s41598-024-65127-9] [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: 02/27/2024] [Accepted: 06/17/2024] [Indexed: 07/06/2024] Open
Abstract
We aimed to investigate the potential impact of metabolic risk factors and lifestyles on mortality in hepatocellular carcinoma (HCC) patients. From the Korean Central Cancer Registry database (2008-2016), 8,505 HCC patients were included in the analysis. Patients with 2 or more metabolic risk factors (n = 2384, 28.0%) showed significantly worse overall survival (OS, 29 months, 95% confidence interval [CI] 27-33) than patients with 0 (n = 2269 [26.7%]; 41 months, 95% CI 37-47), or 1 (n = 3852 [45.3%]; 42 months; 95% CI 38-46) metabolic risk factor. (P < 0.001) In the multivariable Cox analysis, patients with ≥ 2 metabolic risk factors had significantly elevated risk of overall mortality (adjusted hazards ratio (HR) = 1.14 [95% CI 1.06-1.23], P < 0.001) and HCC-specific mortality (sub-distribution HR = 1.09 [95% CI 1.00-1.09], P = 0.046), compared to those without. Alcohol and smoking were also independent risk factors for worse overall and HCC-specific mortality (all P < 0.05). Metabolic comorbidities were associated with greater risk of mortality in a dose-dependent manner in HCC patients, regardless of tumor stage and liver function. Alcohol intake and smoking significantly increased mortality by themselves and even further with the presence of metabolic risk.
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Affiliation(s)
- Hwi Young Kim
- Department of Internal Medicine, College of Medicine, Ewha Womans University, 1071, Anyangcheon-ro, Yangcheon-gu, Seoul, 07985, Republic of Korea.
| | - Hye Ah Lee
- Clinical Trial Center, Ewha Womans University Medical Center, Seoul, Republic of Korea
| | - Pompilia Radu
- University Clinic for Visceral Surgery and Medicine, University of Bern, Inselspital, Bern, Switzerland
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8
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Yang TC, Chen WC, Hou MC, Chen PH, Lee PC, Chang CY, Lu HS, Chen YJ, Hsu SJ, Huang HC, Luo JC, Huang YH, Lee FY. Endoscopic variceal ligation versus propranolol for the primary prevention of oesophageal variceal bleeding in patients with hepatocellular carcinoma: an open-label, two-centre, randomised controlled trial. Gut 2024; 73:682-690. [PMID: 38123994 DOI: 10.1136/gutjnl-2023-330419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Accepted: 11/21/2023] [Indexed: 12/23/2023]
Abstract
OBJECTIVE This randomised trial aimed to address whether endoscopic variceal ligation (EVL) or propranolol (PPL) is more effective at preventing initial oesophageal variceal bleeding (EVB) in patients with hepatocellular carcinoma (HCC). DESIGN Patients with HCC and medium-to-large oesophageal varices (EVs) but without previous EVB were randomised to receive EVL (every 3-4 weeks until variceal eradication) or PPL (up to 320 mg daily) at a 1:1 ratio. Long-term follow-up data on EVB, other upper gastrointestinal bleeding (UGIB), non-bleeding liver decompensation, overall survival (OS) and adverse events (AEs) were analysed using competing risk regression. RESULTS Between June 2011 and April 2021, 144 patients were randomised to receive EVL (n=72) or PPL (n=72). In the EVL group, 7 patients experienced EVB, and 30 died; in the PPL group, 19 patients had EVB, and 40 died. The EVL group had a lower cumulative incidence of EVB (Gray's test, p=0.009) than its counterpart, with no mortality difference (Gray's test, p=0.085). For patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B, EVL was better than PPL in reducing EVB (p<0.001) and mortality (p=0.003). For patients beyond BCLC stage B, between-group outcomes were similar. Other UGIB, non-bleeding liver decompensation and AEs did not differ between groups. A competing risk regression model confirmed the prognostic value of EVL. CONCLUSION EVL is superior to PPL in preventing initial EVB in patients with HCC. The benefits of EVL on EVB and OS may be limited to patients with BCLC stage A/B and not to those with BCLC stage C/D. TRIAL REGISTRATION NUMBER NCT01970748.
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Affiliation(s)
- Tsung-Chieh Yang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Wen-Chi Chen
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Department of Post-Baccalaureate Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ping-Hsien Chen
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Medicine, West Garden Hospital, Taipei, Taiwan
| | - Pei-Chang Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chung-Yu Chang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan
- Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hsiao-Sheng Lu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yu-Jen Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Shao-Jung Hsu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hui-Chun Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jiing-Chyuan Luo
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Fa-Yauh Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan
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Abstract
Globally, hepatocellular carcinoma (HCC) is a major cause of cancer-related death and a leading cause of morbidity and mortality in patients with chronic liver disease and cirrhosis. The predominant cause of HCC is shifting from viral to nonviral causes, in parallel with the high global prevalence of nonalcoholic fatty liver disease and increasing alcohol consumption in many countries. There have been promising recent advances in the treatment of all stages of HCC; however, improvements in early detection, increased utilization of HCC surveillance, and equitable access to HCC therapies are needed to curb increases in HCC mortality.
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Affiliation(s)
- Nicole E Rich
- Division of Digestive and Liver Diseases, Department of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, 5959 Harry Hines Boulevard, Professional Office Building 1, Suite 4.420G, Dallas, TX 75390-8887, USA.
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10
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Hernández-Évole H, Jiménez-Esquivel N, Pose E, Bataller R. Alcohol-associated liver disease: Epidemiology and management. Ann Hepatol 2024; 29:101162. [PMID: 37832648 DOI: 10.1016/j.aohep.2023.101162] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 09/27/2023] [Indexed: 10/15/2023]
Abstract
Alcohol is the leading cause of preventable liver morbidity and mortality worldwide, as it is also the most frequent cause of advanced liver disease. Alcohol-associated liver disease (ALD) covers different phenotypes ranging from steatosis to the development of inflammation (steatohepatitis), fibrosis and ultimately, in a proportion of patients, the development of liver cirrhosis and its associated complications. ALD has a complex pathogenesis that includes the interplay of both genetic and environmental factors, yet the precise mechanisms are largely unknown. Alcohol-associated hepatitis (AH) is a severe clinical presentation of ALD, which is characterized by abrupt jaundice and clinical decompensations of liver disease. AH occurs in a percentage of patients with underlying ALD and active alcohol consumption. Currently, there are no approved targeted therapies able to interfere in the pathogenesis of ALD and halt the progression of the disease, therefore alcohol abstinence is the most effective measure to improve prognosis in this patient population. In this regard, alcohol cessation remains the first-line treatment in all stages of alcohol disease. In patients with advanced ALD nonresponding to medical therapy, liver transplantation is the only approach that improves prognosis, and it should be considered in patients with decompensated cirrhosis. In the last years, AH has emerged as a new indication of early liver transplantation in non-responders to medical therapy, with promising results in highly selected patients. In this review, we provide an update on the epidemiology, risk factors, natural history, diagnosis, pathogenesis, and current treatments for ALD, taking into account the importance of assessing and managing alcohol consumption as the etiological factor and the main driver of prognosis in patients with ALD.
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Affiliation(s)
- Helena Hernández-Évole
- Liver Unit, Hospital Clinic, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Natalia Jiménez-Esquivel
- Liver Unit, Hospital Clinic, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Elisa Pose
- Liver Unit, Hospital Clinic, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Ramón Bataller
- Liver Unit, Hospital Clinic, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
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11
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Huang DQ, Singal AG, Kanwal F, Lampertico P, Buti M, Sirlin CB, Nguyen MH, Loomba R. Hepatocellular carcinoma surveillance - utilization, barriers and the impact of changing aetiology. Nat Rev Gastroenterol Hepatol 2023; 20:797-809. [PMID: 37537332 DOI: 10.1038/s41575-023-00818-8] [Citation(s) in RCA: 42] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/30/2023] [Indexed: 08/05/2023]
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Surveillance for HCC is critical for early detection and treatment, but fewer than one-quarter of individuals at risk of HCC undergo surveillance. Multiple failures across the screening process contribute to the underutilization of surveillance, including limited disease awareness among patients and health-care providers, knowledge gaps, and difficulty recognizing patients who are at risk. Non-alcoholic fatty liver disease and alcohol-associated liver disease are the fastest-rising causes of HCC-related death worldwide and are associated with unique barriers to surveillance. In particular, more than one-third of patients with HCC related to non-alcoholic fatty liver disease do not have cirrhosis and therefore lack a routine indication for HCC surveillance on the basis of current practice guidelines. Semi-annual abdominal ultrasound with measurement of α-fetoprotein levels is recommended for HCC surveillance, but the sensitivity of this approach for early HCC is limited, especially for patients with cirrhosis or obesity. In this Review, we discuss the current status of HCC surveillance and the remaining challenges, including the changing aetiology of liver disease. We also discuss strategies to improve the utilization and quality of surveillance for HCC.
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Affiliation(s)
- Daniel Q Huang
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore.
| | - Amit G Singal
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Fasiha Kanwal
- Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - Pietro Lampertico
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy
- CRC "A. M. and A. Migliavacca" Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Maria Buti
- Liver Unit, Department of Internal Medicine, Hospital Universitari Valle d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
- CIBER-EHD del Instituto Carlos III, Barcelona, Spain
| | - Claude B Sirlin
- Liver Imaging Group, Department of Radiology, UCSD School of Medicine, San Diego, CA, USA
| | - Mindie H Nguyen
- Department of Epidemiology and Population Health, Stanford University Medical Center, Stanford University, Palo Alto, CA, USA
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford University, Palo Alto, CA, USA
| | - Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, San Diego, CA, USA
- Division of Epidemiology, Department of Family Medicine and Public Health, University of California at San Diego, San Diego, CA, USA
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12
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Donati A, Henrion J, Regnier M, Deltenre P, Marot A. Abstinence is associated with better outcomes in patients with alcohol-related hepatocellular carcinoma: Results of an observational study. Clin Res Hepatol Gastroenterol 2023; 47:102225. [PMID: 37838325 DOI: 10.1016/j.clinre.2023.102225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 10/04/2023] [Accepted: 10/11/2023] [Indexed: 10/16/2023]
Abstract
BACKGROUND Patients with alcohol-related cirrhosis and hepatocellular carcinoma (HCC) may have reduced survival compared to those with HCC related to other causes. The impact of abstinence in alcohol-related HCC is unknown. We compared access to curative treatment and the prognosis of patients with HCC according to the cause of cirrhosis and evaluated the impact of abstinence on the prognosis of patients with alcohol-related HCC. PATIENTS AND METHODS Data for patients with cirrhosis and HCC were prospectively collected in a single center. A logistic regression model was used to identify factors associated with access to curative treatment. Multivariate Fine and Gray proportional hazards models were used to identify factors associated with 5-year survival after adjustment for lead-time bias. RESULTS Two hundred patients were included, 114 (57 %) with non-alcohol-related HCC and 86 (43 %) with alcohol-related HCC (35 abstainers, 51 consumers). During follow-up, 21 patients were transplanted and 156 died. The proportion of patients who had access to curative treatment was 65 % in abstainers, 44 % in consumers, and 57 % in patients with non-alcohol-related cirrhosis (p = 0.06). In multivariate analyses, abstinence was not associated with better access to curative treatment. After adjustment for lead-time bias, the 5-year cumulative incidence of overall death was significantly lower in abstainers than in consumers and in patients with non-alcohol-related cirrhosis (52 % vs. 78 % vs. 81 %, respectively, p = 0.04). In multivariate analyses, abstainers had lower risk of death than consumers (SHR: 0.47, 95 % CI: 0.28-0.80, p = 0.005). CONCLUSION Abstinence improves the outcome of patients with alcohol-related cirrhosis once HCC has occurred.
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Affiliation(s)
- Adeline Donati
- Department of Gastroenterology and Hepatology, CHU UCL Namur, Université Catholique de Louvain, Avenue G. Therasse, 1, Yvoir 5530, Belgium
| | - Jean Henrion
- Department of Gastroenterology and Hepatology, Hôpital de Jolimont, Haine-Saint-Paul, Belgium
| | - Maxime Regnier
- Scientific Support Unit (USS), CHU UCL Namur, Université Catholique de Louvain, Yvoir, Belgium
| | - Pierre Deltenre
- Department of Gastroenterology and Hepatology, CHU UCL Namur, Université Catholique de Louvain, Avenue G. Therasse, 1, Yvoir 5530, Belgium; Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; Department of Gastroenterology and Hepatology, Clinique St Luc, Bouge, Belgium
| | - Astrid Marot
- Department of Gastroenterology and Hepatology, CHU UCL Namur, Université Catholique de Louvain, Avenue G. Therasse, 1, Yvoir 5530, Belgium.
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13
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Choi JY, Choi SH, Byun JH, Lee SJ, Kim SY, Won HJ, Shin YM. Liver Imaging Reporting and Data System version 2018 for diagnosing hepatocellular carcinoma in alcoholic liver cirrhosis and virus-related cirrhosis. Eur J Radiol 2023; 168:111139. [PMID: 37856941 DOI: 10.1016/j.ejrad.2023.111139] [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: 05/07/2023] [Revised: 09/01/2023] [Accepted: 10/05/2023] [Indexed: 10/21/2023]
Abstract
PURPOSE We aimed to evaluate and compare the diagnostic performance of Liver Imaging Reporting and Data System (LI-RADS) v2018 for hepatocellular carcinoma (HCC) ≤ 3.0 cm on gadoxetic acid-enhanced MRI according to the etiology of cirrhosis. METHODS Thirty-eight patients with alcoholic liver cirrhosis (ALC) and 37 with hepatitis C virus-related cirrhosis (HCV) who underwent preoperative MRI and subsequent surgical resection or transplantation were included. For comparison groups, patients with hepatitis B virus-related cirrhosis (HBV) were included by 1:1 matching with HCV and ALC groups according to age, lesion size, and Child-Pugh classification. The imaging characteristics of background liver and focal lesions were analyzed. The diagnostic performance of LI-RADS was compared between HCV and HBV groups, and between ALC and HBV groups. RESULTS ALC group showed significantly higher frequency of hepatic steatosis (25.8 % vs. 6.1 %, p =.04) and lower frequency of nonperipheral washout on portal venous-phase in HCC (63.2 % vs. 97.1 %, p <.001) compared with HBV group. ALC group showed significantly lower sensitivity than HBV group (52.6 % vs. 88.6 %, p<.001). No significant differences in diagnostic performance were found between HCV and HBV groups. In ALC group, hepatobiliary-phase hypointensity provided significantly higher sensitivity (76.3 % vs. 52.6 %, p =.008). CONCLUSION The sensitivity of LI-RADS for diagnosing HCC ≤ 3.0 cm was significantly lower in the ALC group than in the HBV group.
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Affiliation(s)
- Ji Young Choi
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Department of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University College of Medicine, Seoul, Republic of Korea
| | - Sang Hyun Choi
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jae Ho Byun
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - So Jung Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hyung Jin Won
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Yong Moon Shin
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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14
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Jacob R, Prince DS, Kench C, Liu K. Alcohol and its associated liver carcinogenesis. J Gastroenterol Hepatol 2023; 38:1211-1217. [PMID: 37263779 DOI: 10.1111/jgh.16248] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 05/22/2023] [Accepted: 05/23/2023] [Indexed: 06/03/2023]
Abstract
Alcohol consumption is a major cause of cirrhosis and hepatocellular carcinoma (HCC). The prevalence of alcohol-associated hepatocellular carcinoma (aHCC) varies worldwide but is highest in Eastern Europe. Alcohol is the second fastest-growing cause of age-standardized liver cancer mortality with tumors more often diagnosed outside surveillance protocols and at a more advanced stage. Risk factors for aHCC include greater amounts of alcohol consumption, sex, and certain genetic polymorphisms. Smoking, concomitant liver disease, obesity, and diabetes act synergistically in increasing the risk of HCC in alcohol-associated liver disease. Alcohol-related hepatocarcinogenesis results from the complex interactions of several mechanistic pathways. Although not completely understood, underlying mechanisms include acetaldehyde-related hepatotoxicity, oxidative stress, activation of the innate immune system, and alterations of the host microbiome.
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Affiliation(s)
- Rachael Jacob
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
| | - David S Prince
- Department of Gastroenterology and Liver, Liverpool Hospital, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, The University of New South Wales, Sydney, New South Wales, Australia
| | - Charlotte Kench
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
| | - Ken Liu
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
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15
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Reggidori N, Bucci L, Santi V, Stefanini B, Lani L, Rampoldi D, Ghittoni G, Farinati F, Masotto A, Stefanini B, Mega A, Biasini E, Foschi FG, Svegliati-Baroni G, Sangiovanni A, Campani C, Raimondo G, Vidili G, Gasbarrini A, Celsa C, Di Marco M, Giannini EG, Sacco R, Brunetto MR, Azzaroli F, Magalotti D, Morisco F, Rapaccini GL, Nardone G, Vitale A, Trevisani F. Landscape of alcohol-related hepatocellular carcinoma in the last 15 years highlights the need to expand surveillance programs. JHEP Rep 2023; 5:100784. [PMID: 37520672 PMCID: PMC10382941 DOI: 10.1016/j.jhepr.2023.100784] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 04/07/2023] [Accepted: 04/13/2023] [Indexed: 08/01/2023] Open
Abstract
BACKGROUND & AIMS Alcohol abuse and metabolic disorders are leading causes of hepatocellular carcinoma (HCC) worldwide. Alcohol-related aetiology is associated with a worse prognosis compared with viral agents, because of the lower percentage of patients diagnosed with HCC under routine surveillance and a higher burden of comorbidity in alcohol abusers. This study aimed to describe the evolving clinical scenario of alcohol-related HCC over 15 years (2006-2020) in Italy. METHODS Data from the Italian Liver Cancer (ITA.LI.CA) registry were used: 1,391 patients were allocated to three groups based on the year of HCC diagnosis (2006-2010; 2011-2015; 2016-2020). Patient characteristics, HCC treatment, and overall survival were compared among groups. Survival predictors were also investigated. RESULTS Approximately 80% of alcohol-related HCCs were classified as cases of metabolic dysfunction-associated fatty liver disease. Throughout the quinquennia, <50% of HCCs were detected by surveillance programmes. The tumour burden at diagnosis was slightly reduced but not enough to change the distribution of the ITA.LI.CA cancer stages. Intra-arterial and targeted systemic therapies increased across quinquennia. A modest improvement in survival was observed in the last quinquennia, particularly after 12 months of patient observation. Cancer stage, HCC treatment, and presence of oesophageal varices were independent predictors of survival. CONCLUSIONS In the past 15 years, modest improvements have been obtained in outcomes of alcohol-related HCC, attributed mainly to underuse of surveillance programmes and the consequent low amenability to curative treatments. Metabolic dysfunction-associated fatty liver disease is a widespread condition in alcohol abusers, but its presence did not show a pivotal prognostic role once HCC had developed. Instead, the presence of oesophageal varices, an independent poor prognosticator, should be considered in patient management and refining of prognostic systems. IMPACT AND IMPLICATIONS Alcohol abuse is a leading and growing cause of hepatocellular carcinoma (HCC) worldwide and is associated with a worse prognosis compared with other aetiologies. We assessed the evolutionary landscape of alcohol-related HCC over 15 years in Italy. A high cumulative prevalence (78%) of metabolic dysfunction-associated fatty liver disease, with signs of metabolic dysfunction, was observed in HCC patients with unhealthy excessive alcohol consumption. The alcohol + metabolic dysfunction-associated fatty liver disease condition tended to progressively increase over time. A modest improvement in survival occurred over the study period, likely because of the persistent underuse of surveillance programmes and, consequently, the lack of improvement in the cancer stage at diagnosis and the patients' eligibility for curative treatments. Alongside the known prognostic factors for HCC (cancer stage and treatment), the presence of oesophageal varices was an independent predictor of poor survival, suggesting that this clinical feature should be carefully considered in patient management and should be included in prognostic systems/scores for HCC to improve their performance.
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Affiliation(s)
- Nicola Reggidori
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Laura Bucci
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Valentina Santi
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Benedetta Stefanini
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Lorenzo Lani
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Davide Rampoldi
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | | | - Fabio Farinati
- Department of Surgery, Oncology, and Gastroenterology, Gastroenterology Unit, University of Padova, Padua, Italy
| | - Alberto Masotto
- Gastroenterology Unit, Ospedale Sacro Cuore Don Calabria, Negrar, Italy
| | - Bernardo Stefanini
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Andrea Mega
- Gastroenterology Unit, Bolzano Regional Hospital, Bolzano, Italy
| | - Elisabetta Biasini
- Infectious Diseases and Hepatology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Francesco Giuseppe Foschi
- Medicina Interna Faenza, Dipartimento Emergenza, Medicina Interna e Cardioloa IRCCS-Istituto Scientifico Romagnolo per lo Studio dei Tumori “Dino Amadori” Meldola, AUSL Romagna, Meldola, Italy
| | - Gianluca Svegliati-Baroni
- Liver Injury and Transplant Unit and Obesity Center, Polytechnic University of Marche, Ancona, Italy
| | - Angelo Sangiovanni
- Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy
| | - Claudia Campani
- Department of Experimental and Clinical Medicine, Internal Medicine and Hepatology Unit, University of Firenze, Florence, Italy
| | - Giovanni Raimondo
- Department of Clinical and Experimental Medicine, Division of Medicine and Hepatology, University of Messina, Messina, Italy
| | - Gianpaolo Vidili
- Department of Medicine, Surgery and Pharmacy, AOU Sassari, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS and Università Cattolica del Sacro Cuore, Rome, Italy
| | - Ciro Celsa
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy
| | | | - Edoardo G. Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
- Gastroenterology Unit, IRCCS Ospedale San Martino, Genoa, Italy
| | - Rodolfo Sacco
- Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, Foggia, Italy
| | | | - Francesco Azzaroli
- Gastroenterology Unit, Department of Surgical and Medical Sciences, IRCCS Azienda Ospedaliero, Universitaria di Bologna, Bologna, Italy
| | - Donatella Magalotti
- Division of Internal Medicine, Neurovascular and Hepatometabolic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Filomena Morisco
- Department of Clinical Medicine and Surgery, Departmental Program “Diseases of the Liver and Biliary System”, University of Napoli “Federico II”, Naples, Italy
| | | | - Gerardo Nardone
- Department of Clinical Medicine and Surgery, Hepato-Gastroenterology Unit, University of Napoli “Federico II”, Naples, Italy
| | - Alessandro Vitale
- Department of Surgical, Oncological, and Gastroenterological Sciences, Hepatobiliary Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
| | - Franco Trevisani
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
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16
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Huang DQ, Tan DJH, Ng CH, Amangurbanova M, Sutter N, Lin Tay PW, Lim WH, Yong JN, Tang A, Syn N, Muthiah MD, Tan EXX, Dave S, Tay B, Majzoub AM, Gerberi D, Kim BK, Loomba R. Hepatocellular Carcinoma Incidence in Alcohol-Associated Cirrhosis: Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2023; 21:1169-1177. [PMID: 35940513 PMCID: PMC10792532 DOI: 10.1016/j.cgh.2022.06.032] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 05/31/2022] [Accepted: 06/25/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Alcohol is one of the leading causes of hepatocellular carcinoma (HCC). However, pooled estimates of HCC incidence in alcohol-associated cirrhosis have not been evaluated systematically. We performed a pooled analysis of time-to-event data to provide robust estimates for the incidence of HCC in alcohol-associated cirrhosis. METHODS Medline, Embase, Cochrane Central Register, Scopus, and Web of Science were searched from inception to August 2021. Individual patient data were reconstructed from published Kaplan-Meier curves, and a pooled analysis of cumulative HCC incidence was performed using a random-effects model. RESULTS We screened 5022 articles and included 18 studies (148,333 patients). In the pooled analysis, the cumulative incidence of HCC in alcohol-associated cirrhosis at 1, 5, and 10 years among studies that accounted for the competing risk of death without HCC was 1%, 3%, and 9%, respectively. A secondary analysis by traditional meta-analysis determined that the HCC incidence rate was higher in cohorts enrolled in a HCC surveillance program (18.6 vs 4.8 per 1000 person-years; P = .001) vs those who were not enrolled in a surveillance program. Meta-regression showed that diabetes, smoking, variceal bleeding, and hepatic decompensation were associated with a higher risk of HCC. CONCLUSIONS Our analysis determined that the 5- and 10- year cumulative risk of HCC in alcohol-associated cirrhosis was 3% and 9%, respectively, with a higher incidence in cohorts that were enrolled in a HCC surveillance program. These data should be validated further in large prospective studies, and may have important implications for HCC screening and surveillance among patients with alcohol-associated cirrhosis.
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Affiliation(s)
- Daniel Q Huang
- NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, California; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore.
| | - Darren J H Tan
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Cheng Han Ng
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Maral Amangurbanova
- NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, California
| | - Nancy Sutter
- NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, California
| | - Phoebe Wen Lin Tay
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Wen Hui Lim
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jie Ning Yong
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Ansel Tang
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Nicholas Syn
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Mark D Muthiah
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore
| | - Eunice X X Tan
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore
| | - Shravan Dave
- NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, California
| | - Benjamin Tay
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore
| | - Abdul M Majzoub
- Division of Internal Medicine, Conemaugh Memorial Medical Center, Johnstown, Pennsylvania
| | | | - Beom Kyung Kim
- NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, California; Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, California.
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17
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Mathurin P, de Zélicourt M, Laurendeau C, Dhaoui M, Kelkouli N, Blanc JF. Treatment patterns, risk factors and outcomes for patients with newly diagnosed hepatocellular carcinoma in France: a retrospective database analysis. Clin Res Hepatol Gastroenterol 2023; 47:102124. [PMID: 37061035 DOI: 10.1016/j.clinre.2023.102124] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 03/21/2023] [Accepted: 04/12/2023] [Indexed: 04/17/2023]
Abstract
BACKGROUND & AIMS The aim of this analysis was to describe the nationwide distribution of patients with newly diagnosed Hepatocellular carcinoma (HCC) according to treatment pattern, aetiologies, and outcomes in France. METHOD A retrospective cohort of patients with newly diagnosed HCC was selected over the period 2015-2017 in a French claims database covering 99% of the population. Treatment pattern was described using an algorithm based on a ranking of curative and palliative HCC treatments identified. Survival was analyzed using Kaplan-Meier curves according to major treatments and aetiologies. RESULTS A total of 20,083 incident patients were identified with a mean age of 69.2 years (SD: 11.0) and 82.4% of men. The mean duration of follow-up was 10.0 months (SD: 9.7). At least one HCC risk factor could be identified in 87.0% of patients. The most frequent aetiologies were alcohol-related liver disease present in 50.8% of patients, a metabolic disease (NAFLD, NASH or diabetes) without alcohol or viral hepatitis (44.5%) and viral hepatitis (20.0%). Only 32.7% of patients received a curative therapy, with a 1-year survival of 89.5%, while 38.0% of patients received only best supportive care, with a 1-year survival of 12.9%. The highest rates of curative treatments were found in patients with viral hepatitis, associated or not with another risk factor. CONCLUSION Hepatocellular carcinoma was still most often diagnosed at an advanced disease stage as shown by the low rate of curative treatment observed and the very poor prognosis. Viral hepatic aetiology was associated with the best survival.
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Affiliation(s)
- Philippe Mathurin
- Hôpital Claude Huriez, Centre Hospitalier Universitaire de Lille, Lille, France
| | | | | | | | | | - Jean-Frédéric Blanc
- Hôpital Haut Lévêque, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
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18
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Calderon-Martinez E, Landazuri-Navas S, Vilchez E, Cantu-Hernandez R, Mosquera-Moscoso J, Encalada S, Al lami Z, Zevallos-Delgado C, Cinicola J. Prognostic Scores and Survival Rates by Etiology of Hepatocellular Carcinoma: A Review. J Clin Med Res 2023; 15:200-207. [PMID: 37187717 PMCID: PMC10181349 DOI: 10.14740/jocmr4902] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 04/14/2023] [Indexed: 05/17/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a common cancer and ranks sixth among all malignancies worldwide. Risk factors for HCC can be classified as infectious or behavioral. Viral hepatitis and alcohol abuse are currently the most common risk factors for HCC; however, nonalcoholic liver disease is expected to become the most common cause of HCC in upcoming years. HCC survival rates vary according to the causative risk factors. As in any malignancy, staging is crucial in making therapeutic decisions. The selection of a specific score should be individualized according to patient characteristics. In this review, we summarize the current data on epidemiology, risk factors, prognostic scores, and survival in HCC.
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Affiliation(s)
| | | | | | - Raul Cantu-Hernandez
- Department of Internal Medicine, Monterrey Institute of Technology and Higher Studies, Mexico
| | | | - Sebastian Encalada
- Department of Internal Medicine, University of the Americas, Quito, Ecuador
| | - Zahraa Al lami
- Department of Internal Medicine, University of Baghdad, College of Medicine, Iraq
| | | | - John Cinicola
- Department of Internal Medicine, UPMC Harrisburg, Harrisburg, PA, USA
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19
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Šafčák D, Dražilová S, Gazda J, Andrašina I, Adamcová-Selčanová S, Barila R, Mego M, Rác M, Skladaný Ľ, Žigrai M, Janičko M, Jarčuška P. Alcoholic Liver Disease-Related Hepatocellular Carcinoma: Characteristics and Comparison to General Slovak Hepatocellular Cancer Population. Curr Oncol 2023; 30:3557-3570. [PMID: 36975484 PMCID: PMC10047624 DOI: 10.3390/curroncol30030271] [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: 02/09/2023] [Revised: 03/13/2023] [Accepted: 03/15/2023] [Indexed: 03/29/2023] Open
Abstract
Hepatocellular carcinoma (HCC) has multiple molecular classes that are associated with distinct etiologies and, besides particular molecular characteristics, that also differ in clinical aspects. We aim to characterize the clinical aspects of alcoholic liver disease-related HCC by a retrospective observational study that included all consequent patients diagnosed with MRI or histologically verified HCC in participating centers from 2010 to 2016. A total of 429 patients were included in the analysis, of which 412 patients (96%) had cirrhosis at the time of diagnosis. The most common etiologies were alcoholic liver disease (ALD) (48.3%), chronic hepatitis C (14.9%), NAFLD (12.6%), and chronic hepatitis B (10%). Patients with ALD-related HCC were more commonly males, more commonly had cirrhosis that was in more advanced stages, and had poorer performance status. Despite these results, no differences were observed in the overall (median 8.1 vs. 8.5 months) and progression-free survival (median 4.9 vs. 5.7 months). ALD-HCC patients within BCLC stage 0-A less frequently received potentially curative treatment as compared to the control HCC patients (62.2% vs. 87.5%, p = 0.017); and in patients with ALD-HCC liver function (MELD score) seemed to have a stronger influence on the prognosis compared to the control group HCC. Systemic inflammatory indexes were strongly associated with survival in the whole cohort. In conclusion, alcoholic liver disease is the most common cause of hepatocellular carcinoma in Slovakia, accounting for almost 50% of cases; and patients with ALD-related HCC more commonly had cirrhosis that was in more advanced stages and had poorer performance status, although no difference in survival between ALD-related and other etiology-related HCC was observed.
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Affiliation(s)
- Dominik Šafčák
- Department of Radiotherapy and Oncology, East Slovakia Institute of Oncology, 04191 Košice, Slovakia
- 2nd Department of Internal Medicine, Louis Pasteur University Hospital, 04011 Košice, Slovakia
| | - Sylvia Dražilová
- 2nd Department of Internal Medicine, Louis Pasteur University Hospital, 04011 Košice, Slovakia
- Department of Internal Medicine, Faculty of Medicine, Pavol Jozef Safarik University in Kosice, 04011 Košice, Slovakia
| | - Jakub Gazda
- 2nd Department of Internal Medicine, Louis Pasteur University Hospital, 04011 Košice, Slovakia
- Department of Internal Medicine, Faculty of Medicine, Pavol Jozef Safarik University in Kosice, 04011 Košice, Slovakia
| | - Igor Andrašina
- Department of Radiotherapy and Oncology, East Slovakia Institute of Oncology, 04191 Košice, Slovakia
| | | | - Radovan Barila
- Oncological Cluster, Saint Michael Hospital Michalovce, 07101 Michalovce, Slovakia
| | - Michal Mego
- Department of Clinical Oncology, National Oncology Institute of Slovakia, 83310 Bratislava, Slovakia
| | - Marek Rác
- Department of Internal Medicine, University Hospital Nitra, 94901 Nitra, Slovakia
| | - Ľubomír Skladaný
- Department of Internal Medicine, F.D. Roosevelt University Hospital, 97517 Banská Bystrica, Slovakia
| | - Miroslav Žigrai
- Department of Internal Medicine, University Hospital in Bratislava, 83101 Bratislava, Slovakia
| | - Martin Janičko
- 2nd Department of Internal Medicine, Louis Pasteur University Hospital, 04011 Košice, Slovakia
- Department of Internal Medicine, Faculty of Medicine, Pavol Jozef Safarik University in Kosice, 04011 Košice, Slovakia
| | - Peter Jarčuška
- 2nd Department of Internal Medicine, Louis Pasteur University Hospital, 04011 Košice, Slovakia
- Department of Internal Medicine, Faculty of Medicine, Pavol Jozef Safarik University in Kosice, 04011 Košice, Slovakia
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20
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Surgical resection versus transarterial chemoembolization followed by moderately hypofractionated radiotherapy in hepatocellular carcinoma. Strahlenther Onkol 2023; 199:293-303. [PMID: 36441171 DOI: 10.1007/s00066-022-02022-0] [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: 07/25/2022] [Accepted: 10/17/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND AND OBJECTIVE Transarterial chemoembolization (TACE) is the gold standard treatment in intermediate hepatocellular carcinoma (HCC), but long-term disease control rates remain low. Herein, we compared results of TACE followed by hypofractionated radiotherapy (TACE-hRT) to surgical resection (SR) in early single or paucinodular intrahepatic HCC. METHODS Between June 2004 and November 2016, data on 160 consecutive patients with Barcelona Clinic Liver Cancer (BCLC) stage A Child-Pugh A HCC treated with SR or TACE-hRT in our expert center were retrospectively reviewed. Time to progression (TTP), progression-free survival (PFS), and overall survival (OS) were evaluated. Clinical outcomes were compared using the stabilized-weights inverse probability of treatment weighting propensity score. RESULTS Ninety-eight patients underwent SR and 62 were treated by TACE-hRT. Median total dose of RT was 54 Gy (interquartile range [IQR] 54-54) in 3‑Gy fractions. Median OS follow-up was 93 months. TTP did not significantly differ between patients following SR and TACE-hRT, with 1‑year rates of 68.2% and 82.6% (p = 0.17), respectively. In contrast, PFS and OS were lower in the TACE-hRT group (p = 0.015 and p = 0.006), with a median OS of 37 vs. 63 months for patients with surgery and TACE-hRT, respectively. In multivariate analysis, a significant negative impact on PFS and OS was seen for age at diagnosis, on TTP for alcohol-related liver disease, and on OS for total number of HCC nodules. Symptomatic grade ≥ 3 adverse events were presented by 42 (42.9%) SR and 19 (30.6%) TACE-hRT patients (p = 0.17). CONCLUSION In patients presenting Child-Pugh A BCLC‑A HCC with high risk for surgical complications, TACE-hRT can be an effective and safe treatment. However, surgical management remains the standard of care whenever possible.
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21
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An Overview of Hepatocellular Carcinoma Surveillance Focusing on Non-Cirrhotic NAFLD Patients: A Challenge for Physicians. Biomedicines 2023; 11:biomedicines11020586. [PMID: 36831120 PMCID: PMC9953185 DOI: 10.3390/biomedicines11020586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Revised: 02/08/2023] [Accepted: 02/09/2023] [Indexed: 02/18/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide and it ranges from simple steatosis to hepatocellular carcinoma (HCC). HCC represents the first liver tumor and the third source of cancer death. In the next few years, the prevalence of NAFLD and consequently of HCC is estimated to increase, becoming a major public health problem. The NAFLD-HCC shows several differences compared to other causes of chronic liver disease (CLD), including the higher percentage of patients that develop HCC in the absence of liver cirrhosis. In HCC surveillance, the international guidelines suggest a six months abdominal ultrasound (US), with or without alpha-fetoprotein (AFP) evaluation, in patients with cirrhosis and in a subgroup of patients with chronic hepatitis B infection. However, this screening program reveals several limitations, especially in NAFLD patients. Thus, new biomarkers and scores have been proposed to overcome the limits of HCC surveillance. In this narrative review we aimed to explore the differences in the HCC features between NAFLD and non-NAFLD patients, and those between NAFLD-HCC developed in the cirrhotic and non-cirrhotic liver. Finally, we focused on the limits of tumor surveillance in NAFLD patients, and we explored the new biomarkers for the early diagnosis of HCC.
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22
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Huang DQ, Mathurin P, Cortez-Pinto H, Loomba R. Global epidemiology of alcohol-associated cirrhosis and HCC: trends, projections and risk factors. Nat Rev Gastroenterol Hepatol 2023; 20:37-49. [PMID: 36258033 PMCID: PMC9579565 DOI: 10.1038/s41575-022-00688-6] [Citation(s) in RCA: 217] [Impact Index Per Article: 108.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/08/2022] [Indexed: 02/07/2023]
Abstract
Heavy alcohol consumption is a major cause of morbidity and mortality. Globally, alcohol per-capita consumption rose from 5.5 litres in 2005 to 6.4 litres in 2016 and is projected to increase further to 7.6 litres in 2030. In 2019, an estimated 25% of global cirrhosis deaths were associated with alcohol. The global estimated age-standardized death rate (ASDR) of alcohol-associated cirrhosis was 4.5 per 100,000 population, with the highest and lowest ASDR in Africa and the Western Pacific, respectively. The annual incidence of hepatocellular carcinoma (HCC) among patients with alcohol-associated cirrhosis ranged from 0.9% to 5.6%. Alcohol was associated with approximately one-fifth of global HCC-related deaths in 2019. Between 2012 and 2017, the global estimated ASDR for alcohol-associated cirrhosis declined, but the ASDR for alcohol-associated liver cancer increased. Measures are required to curb heavy alcohol consumption to reduce the burden of alcohol-associated cirrhosis and HCC. Degree of alcohol intake, sex, older age, obesity, type 2 diabetes mellitus, gut microbial dysbiosis and genetic variants are key factors in the development of alcohol-associated cirrhosis and HCC. In this Review, we discuss the global epidemiology, projections and risk factors for alcohol-associated cirrhosis and HCC.
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Affiliation(s)
- Daniel Q Huang
- NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, San Diego, CA, USA
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
| | - Philippe Mathurin
- Service des Maladies de l'appareil digestif, Hôpital Huriez, Lille, France
- Unité INSERM 995, Faculté de médecine, Lille, France
| | - Helena Cortez-Pinto
- Clínica Universitária de Gastrenterologia, Faculdade de Medicina, Departamento de Gastrenterologia, Centro Hospitalar Lisboa Norte, Lisboa, Portugal
| | - Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, San Diego, CA, USA.
- Division of Epidemiology, Department of Family Medicine and Public Health, University of California at San Diego, San Diego, CA, USA.
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23
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Hernandez-Tejero M, Clemente-Sanchez A, Bataller R. Spectrum, Screening, and Diagnosis of Alcohol-related Liver Disease. J Clin Exp Hepatol 2023; 13:75-87. [PMID: 36647416 PMCID: PMC9840079 DOI: 10.1016/j.jceh.2022.10.002] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Accepted: 10/02/2022] [Indexed: 11/06/2022] Open
Abstract
Alcohol-related liver disease (ALD) represents one of the leading causes of chronic liver disease and is a major cause of liver-related deaths worldwide. ALD encompasses a range of disorders including simple steatosis, alcoholic steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Patients with underlying ALD and continued heavy alcohol consumption can also develop an episode of acute-on-chronic liver injury called alcohol-associated hepatitis, the most severe form of the disease, which portends a poor prognosis. The most important risk factor for the development of ALD is the amount of alcohol consumed. Individual susceptibility to progression to advanced fibrosis among heavy drinkers is likely determined by a combination of behavioral, environmental, genetic, and epigenetic factors, but the mechanisms are largely unknown. The only effective therapy for ALD is prolonged alcohol abstinence. Diagnosis of ALD involves assessing patients for alcohol use disorder and signs of advanced liver disease. In clinical practice, the histological assessment for ALD diagnosis is uncommon, and it is usually based on the medical history, clinical manifestations, and laboratory and imaging tests. Several promising biomarkers that can have both diagnostic and prognostic value in patients with ALD have been identified in recent years. This review provides an overview of the clinical spectrum of ALD, the diagnostic approach of the disease from different perspectives as well as current diagnostic and prognostic biomarkers.
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Key Words
- AH, alcohol-associated hepatitis
- ALD, alcohol-related liver disease
- ASH, alcoholic steatohepatitis
- AST, aspartate aminotransferase
- AUD, alcohol use disorder
- AUDIT, Alcohol Use Disorders Identification Test
- CAGE, Cut down, Annoyed, Guilty, and Eye-opener
- DSM-5, Diagnostic and Statistical Manual of Mental Disorders Fifth edition
- GGT, gamma-glutamyl transferase
- HCC, hepatocellular carcinoma
- INR, international normalized ratio
- LSM, liver stiffness measurement
- NAFLD, non-alcoholic fatty liver disease
- PCF, pericellular fibrosis
- SFS, SALVE fibrosis stages
- SHG, SALVE Histopathology Group
- TE, transient elastography
- WHO, World Health Organization
- alcohol-associated hepatitis
- alcohol-related liver cirrhosis
- alcohol-related liver disease
- alcoholic steatohepatitis
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Affiliation(s)
- Maria Hernandez-Tejero
- Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Center for Liver Diseases, Pittsburgh Liver Research Center, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, 200 Lothrop St, Pittsburgh, PA 15213, USA
| | - Ana Clemente-Sanchez
- Liver Unit, Digestive Department, Hospital General Universitario Gregorio Marañón, Complutense University of Madrid, CIBERehd, Madrid, Spain
- Center for Liver Diseases, Pittsburgh Liver Research Center, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, 200 Lothrop St, Pittsburgh, PA 15213, USA
| | - Ramon Bataller
- Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Center for Liver Diseases, Pittsburgh Liver Research Center, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, 200 Lothrop St, Pittsburgh, PA 15213, USA
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24
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Luo PQ, Ye ZH, Zhang LX, Song ED, Wei ZJ, Xu AM, Lu Z. Prognostic factors for disease-free survival in postoperative patients with hepatocellular carcinoma and construction of a nomogram model. World J Clin Cases 2022; 10:13250-13263. [PMID: 36683638 PMCID: PMC9850999 DOI: 10.12998/wjcc.v10.i36.13250] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 09/15/2022] [Accepted: 11/25/2022] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the most common type of liver cancer and has a high risk of invasion and metastasis along with a poor prognosis.
AIM To investigate the independent predictive markers for disease-free survival (DFS) in patients with HCC and establish a trustworthy nomogram.
METHODS In this study, 445 patients who were hospitalized in The First Affiliated Hospital of Anhui Medical College between December 2009 and December 2014 were retrospectively examined. The survival curve was plotted using the Kaplan–Meier method and survival was determined using the log-rank test. To identify the prognostic variables, multivariate Cox regression analyses were carried out. To predict the DFS in patients with HCC, a nomogram was created. C-indices and receiver operator characteristic curves were used to evaluate the nomogram's performance. Decision curve analysis (DCA) was used to evaluate the clinical application value of the nomogram.
RESULTS Longer DFS was observed in patients with the following characteristics: elderly, I–II stage, and no history of hepatitis B. The calibration curve showed that this nomogram was reliable and had a higher area under the curve value than the tumor node metastasis (TNM) stage. Moreover, the DCA curve revealed that the nomogram had good clinical applicability in predicting 3- and 5-year DFS in HCC patients after surgery.
CONCLUSION Age, TNM stage, and history of hepatitis B infection were independent factors for DFS in HCC patients, and a novel nomogram for DFS of HCC patients was created and validated.
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Affiliation(s)
- Pan-Quan Luo
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230031, Anhui Province, China
| | - Zheng-Hui Ye
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230031, Anhui Province, China
| | - Li-Xiang Zhang
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230031, Anhui Province, China
| | - En-Dong Song
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230031, Anhui Province, China
| | - Zhi-Jian Wei
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230031, Anhui Province, China
| | - A-Man Xu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230031, Anhui Province, China
| | - Zhen Lu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230011, Anhui Province, China
- Anhui Public Health Clinical Center, Hefei 230011, Anhui Province, China
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25
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Huang DQ, Tran A, Tan EX, Nerurkar SN, Teh R, Teng MLP, Yeo EJ, Zou B, Wong C, Esquivel CO, Bonham CA, Nguyen MH. Characteristics and outcomes of hepatocellular carcinoma patients with macrovascular invasion following surgical resection: a meta-analysis of 40 studies and 8,218 patients. Hepatobiliary Surg Nutr 2022; 11:848-860. [PMID: 36523924 PMCID: PMC9745615 DOI: 10.21037/hbsn-21-419] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Accepted: 03/23/2022] [Indexed: 08/05/2023]
Abstract
Background Guidelines recommend that hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) and/or hepatic vein tumor thrombosis (HVTT) should undergo systemic therapy. However, recent data suggest that surgical resection may be beneficial in selected cases, but outcomes are heterogenous. We aimed to estimate pooled overall survival (OS), recurrence free survival (RFS) and complication rates in HCC patients with macrovascular invasion (MVI) following surgical resection. Methods In this systematic review and meta-analysis, two investigators independently searched PubMed, Embase, and Cochrane databases from inception to Nov 10, 2020, without language restrictions, for studies reporting outcomes of adult HCC patients with MVI who underwent liver resection with curative intent. Results We screened 8,598 articles and included 40 studies involving 8,218 patients. Among all patients with MVI, the pooled median OS was 14.39 months [95% confidence interval (CI): 10.99-18.84], 1-year OS was 54.47% (95% CI: 46.12-62.58%) and 3-year OS was 23.20% (95% CI: 16.61-31.42%). Overall, 1- and 3-year RFS were 27.70% (95% CI: 21.00-35.57%) and 10.06% (95% CI: 6.62-15.01%), respectively. Among patients with PVTT, median OS was 20.41 months in those with segmental/2nd order involvement compared to 12.91 months if 1st order branch was involved and 6.41 months if the main trunk was involved. The pooled rate of major complications was 6.17% (95% CI: 3.53-10.56%). Conclusions Overall median survival was 14.39 months for HCC patients with MVI following resection. Median survival was higher in PVTT with segmental/2nd order involvement at 20.41 versus 6.41 months if the main trunk was involved.
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Affiliation(s)
- Daniel Q. Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | | | - Eunice X. Tan
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Sanjna N. Nerurkar
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Readon Teh
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Margaret L. P. Teng
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Ee Jin Yeo
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
- Adelaide Medical School, The University of Adelaide, Adelaide, Australia
| | - Biyao Zou
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA
- Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, USA
| | - Connie Wong
- Lane Medical Library, Stanford University School of Medicine, Stanford, CA, USA
| | - Carlos O. Esquivel
- Division of Abdominal Transplantation, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - C. Andrew Bonham
- Division of Abdominal Transplantation, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Mindie H. Nguyen
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA
- Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, USA
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26
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The efficacy of contrast-enhanced computed tomography on the management of gastroesophageal varices in patients with hepatocellular carcinoma. Sci Rep 2022; 12:20726. [PMID: 36456830 PMCID: PMC9715668 DOI: 10.1038/s41598-022-25350-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Accepted: 11/29/2022] [Indexed: 12/03/2022] Open
Abstract
The screening of gastroesophageal varices (GEV) is critical in hepatocellular carcinoma (HCC) management. Contrast-enhanced computed tomography (CECT) is often performed in patients with HCC. Therefore, this study aimed to examine the use of CECT in screening for GEV and predicting GEV bleeding. This retrospective study enrolled 312 consecutive patients who are initially diagnosed with HCC, measured the lower esophageal (EIV) and fundal intramural vessel (FIV) diameter on CECT, examined the changes after 1, 2, and 3 years, and verified the relationship with GEV bleeding. The EIV and FIV diameter on CECT correlates well with endoscopic variceal classification. EIV significantly worsened after 2 and 3 years. FIV showed worsening at both 1, 2, and 3 years. Cumulative GEV bleeding rates were 3.7% at 1 year and 6.2% at 3 years. The multivariate analysis revealed that EIV, FIV, and portal vein tumor thrombus were associated with GEV bleeding. Furthermore, EIV deterioration at 1, 2, and 3 years correlated with GEV bleeding. In conclusion, CECT is useful in variceal management during the longitudinal clinical course of HCC, and has the potential to decrease screening endoscopy. With deterioration in EIV, treatments should be considered due to a high-risk GEV bleeding.
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27
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Yang WJ, Kang D, Song MG, Seo TS, Kim JH. The Impact of Socioeconomic Status on Mortality in Patients with Hepatocellular Carcinoma: A Korean National Cohort Study. Gut Liver 2022; 16:976-984. [PMID: 35466091 PMCID: PMC9668501 DOI: 10.5009/gnl210567] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 01/06/2022] [Accepted: 01/18/2022] [Indexed: 11/04/2022] Open
Abstract
Background/Aims We studied the impact of socioeconomic status (SES) on mortality in hepatocellular carcinoma patients and analyzed the effect of SES on initial treatment allocation. Methods A cohort study was conducted using data from the National Health Insurance Service- National Sample Cohort of Korea. A total of 3,032 hepatocellular carcinoma patients who were newly diagnosed between January 2003 and December 2013 were included. Income level was categorized as Medical Aid and ≤30th, 31st-70th, or >70th percentile as an SES indicator. Results The proportion of Medical Aid was 4.3%. The highest risks of all-cause mortality associated with Medical Aid were evident in the transcatheter arterial chemoembolization group (fully adjusted hazard ratio [HR], 2.40; 95% confidence interval [CI], 1.25 to 4.58), the other treatments group (fully adjusted HR, 2.86; 95% CI, 1.85 to 4.41), and the no treatment group (fully adjusted HR, 2.69; 95% CI, 1.79 to 4.04) but not in the curative treatment group. An association between the lower-income percentile and higher liver cancer-specific mortality was also observed, except in the curative treatment group. The association between income percentile and all-cause mortality was nonlinear, with a stronger association in the lower-income percentiles than in the higher income percentiles (p-value for nonlinear spline terms <0.05). Conclusions Patients in the lower SES group, especially patients not eligible for curative treatment, had an increased risk of mortality. In addition, the association between SES and the risk for mortality was stronger in the lower-income percentile than in the moderate to higher income percentiles.
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Affiliation(s)
- Woo Jin Yang
- Department of Radiology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Danbee Kang
- Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Korea
| | - Myung Gyu Song
- Department of Radiology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Tae-Seok Seo
- Department of Radiology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Ji Hoon Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
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Ueda S, Hori S, Hori A, Makitani K, Wan K, Sonomura T. Retrospective Study of the Efficacy and Safety of Chemoembolization with Drug-Eluting Microspheres Combined with Intra-Arterial Infusion of Bevacizumab for Unresectable Hepatocellular Carcinoma. J Hepatocell Carcinoma 2022; 9:973-985. [PMID: 36117527 PMCID: PMC9480604 DOI: 10.2147/jhc.s380439] [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] [Received: 06/29/2022] [Accepted: 09/09/2022] [Indexed: 11/23/2022] Open
Abstract
Purpose To evaluate the efficacy and safety of chemoembolization with drug-eluting microspheres (DEM-TACE) combined with intra-arterial infusion of bevacizumab in patients with unresectable hepatocellular carcinoma (uHCC) and to identify possible prognostic factors. Patients and Methods Between November 2014 and December 2020, 34 patients underwent DEM-TACE combined with intra-arterial infusion of bevacizumab for Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) beyond the Up-to-seven criteria or BCLC stage C HCC. Patients with extrahepatic metastasis or inferior vena cava invasion were excluded. The primary endpoint was overall survival (OS). The secondary endpoints were safety (assessed using Common Terminology Criteria for Adverse Events v5.0), the response rate at 1 month, and the identification of prognostic factors. The median OS was calculated using the Kaplan-Meier method. The response rate was evaluated according to the modified Response Evaluation Criteria in Solid Tumors. Prognostic factors were investigated by univariate and multivariable analysis using the Cox proportional hazards model. Results The median OS was 13 months. BCLC stage and presence of portal vein invasion were not significantly associated with OS. There were no grade ≥3 adverse events. The Child-Pugh class did not decline after treatment in 31 of 34 patients. The overall response rate was 14.2% and the disease control rate was 100%. Significant prognostic factors were alcoholic liver disease, Child-Pugh score of ≥8, and microsphere size of 50-100 μm. Conclusion DEM-TACE combined with intra-arterial infusion of bevacizumab is safe and effective, and it could be a treatment option for unresectable HCCs.
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Affiliation(s)
- Shota Ueda
- Department of Radiology, Wakayama Medical University, Wakayama, Japan
| | - Shinichi Hori
- Department of Radiology, Institute for Image Guided Therapy, Izumisano City, Osaka, Japan
| | - Atsushi Hori
- Department of Radiology, Institute for Image Guided Therapy, Izumisano City, Osaka, Japan
| | - Kazuhiro Makitani
- Department of Radiology, Institute for Image Guided Therapy, Izumisano City, Osaka, Japan
| | - Ke Wan
- Clinical Study Support Center, Wakayama Medical University Hospital, Wakayama, Japan
| | - Tetsuo Sonomura
- Department of Radiology, Wakayama Medical University, Wakayama, Japan
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Costentin CE, Minoves M, Kotzki S, Farges O, Goutté N, Decaens T, Bailly S. Alcohol-related hepatocellular carcinoma is a heterogenous condition: Lessons from a latent class analysis. Liver Int 2022; 42:1638-1647. [PMID: 35324065 PMCID: PMC9373918 DOI: 10.1111/liv.15256] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 03/06/2022] [Accepted: 03/13/2022] [Indexed: 02/13/2023]
Abstract
BACKGROUND Alcohol-associated hepatocellular carcinoma (AL-HCC) poor prognosis has been attributed to diagnosis at a later stage. However, host factors and specific health trajectories have been associated with severe outcomes in alcohol-related liver disease. We hypothesize AL-HCC is not a homogeneous condition but encompasses subgroups yielding different outcomes. AIMS Our aim was to provide a first attempt at a clinical phenotyping of AL-HCC. METHODS We analysed data for the calendar years 2007-2013 from the French nationwide administrative hospital database. We selected patients with AL-HCC only. Clustering of AL-HCC phenotypes was performed by latent class analysis (LCA). RESULTS The study included 11 363 patients with AL-HCC, mainly male (89.6%), median age 67 years [IQR: 61; 74] of which 71.2% had at least one metabolic comorbidity. Five phenotypes were identified. Phenotype 1 (41.4%) displayed high rates of unrecognized cirrhosis prior to HCC diagnosis (81%), low rates of metabolic comorbidities (diabetes 13%), and mostly compensated liver disease at HCC diagnosis while the four other phenotypes displayed high rates of metabolic comorbidities (diabetes up to 100%), various patterns of liver disease trajectories and overall 42% unrecognized cirrhosis. In adjusted survival analysis, compared to phenotype 1, risk of death after HCC diagnosis was significantly different for all phenotypes. CONCLUSION LCA uncovers AL-HCC is a heterogeneous condition with distinct phenotypes yielding specific survival outcomes. Frequent unrecognized cirrhosis prior to HCC underlines the urgent need for implementing strategies to identify the underlying liver disease prior to HCC onset in patients with documented alcohol use disorders and metabolic comorbidities.
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Affiliation(s)
- Charlotte E. Costentin
- Institute for Advanced Biosciences, INSERM U1209/CNRS UMRGrenoble Alpes UniversityGrenobleFrance,Hepatology, gastro‐enterology and digestive oncologyGrenoble Alpes University HospitalLa TroncheFrance
| | - Mélanie Minoves
- HP2 Laboratory, INSERM U1300 and Grenoble Alpes University HospitalGrenoble Alpes UniversityGrenobleFrance,Department of PharmacyGrenoble Alpes University HospitalLa TroncheFrance
| | - Sylvain Kotzki
- HP2 Laboratory, INSERM U1300 and Grenoble Alpes University HospitalGrenoble Alpes UniversityGrenobleFrance
| | - Olivier Farges
- Hepato‐Biliary Surgery DepartmentBeaujon HospitalClichyFrance
| | - Nathalie Goutté
- INSERM UMRS‐1193, DHU Hépatinov and Centre Hépatobiliaire, Paul‐Brousse Hospital, Assistance Publique – Hôpitaux de Paris VillejuifParis‐Saclay University et DHU Hépatinov par FHU HépatinovVillejuifFrance
| | - Thomas Decaens
- Institute for Advanced Biosciences, INSERM U1209/CNRS UMRGrenoble Alpes UniversityGrenobleFrance,Hepatology, gastro‐enterology and digestive oncologyGrenoble Alpes University HospitalLa TroncheFrance
| | - Sébastien Bailly
- HP2 Laboratory, INSERM U1300 and Grenoble Alpes University HospitalGrenoble Alpes UniversityGrenobleFrance
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Rattanasupar A, Chang A, Prateepchaiboon T, Pungpipattrakul N, Akarapatima K, Songjamrat A, Pakdeejit S, Prachayakul V, Piratvisuth T. Impact of alcohol consumption on treatment outcome of hepatocellular carcinoma patients with viral hepatitis who underwent transarterial chemoembolization. World J Hepatol 2022; 14:1162-1172. [PMID: 35978671 PMCID: PMC9258258 DOI: 10.4254/wjh.v14.i6.1162] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 04/24/2022] [Accepted: 06/13/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Alcohol consumption increases the risk of hepatocellular carcinoma (HCC) in patients with pre-existing liver disease, including viral hepatitis. However, studies on the impact of alcohol consumption on the outcomes of HCC are limited. We hypothesized that alcohol had an additional effect with chronic viral hepatitis infection on treatment outcomes after transarterial chemoembolization (TACE) in patients with intermediate-stage HCC (Barcelona Clinical Liver Cancer [BCLC] -B).
AIM To evaluate the additional effect of alcohol on treatment outcomes of TACE among HCC patients with viral hepatitis.
METHODS This study, conducted at Hatyai Hospital in Thailand, included HCC patients over 18 years of age with chronic viral hepatitis. Records of HCC patients with viral hepatitis classified as BCLC-B who underwent TACE as the first treatment modality between 2014 and 2019 were retrospectively reviewed. Patients with chronic viral hepatitis only were categorized under group A, and those with chronic viral hepatitis and concurrent alcohol consumption were categorized under group B. Both groups were compared, and the Cox proportional-hazards model was used to identify the survival-influencing variables.
RESULTS Of the 69 patients, 53 were categorized in group A and 16 in group B. There were no statistically significant differences in tumor characteristics between the two patient groups. However, Group A had a statistically significantly higher proportion of complete response (24.5% vs 0%, P = 0.030) and a higher median survival rate (26.2 mo vs 8.4 mo; log-rank P = 0.012) compared to group B. Factors associated with decreased survival in the proportional-hazards model included alcohol consumption (hazards ratio [HR], 2.377; 95% confidence interval [CI], 1.109-5.095; P = 0.026), presence of portal hypertension (HR, 2.578; 95%CI, 1.320–5.037; P = 0.006), largest tumor size > 5 cm (HR, 3.558; 95%CI, 1.824-6.939; P < 0.001), and serum alpha-fetoprotein level > 100 ng/mL (HR, 2.536; 95%CI, 1.377-4.670; P = 0.003).
CONCLUSION In HCC BCLC B patients with chronic viral hepatitis, alcohol consumption is an independent risk factor for increased mortality and decreases the rate of complete response and survival after TACE.
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Affiliation(s)
- Attapon Rattanasupar
- Division of Gastroenterology, Department of Internal Medicine, Hatyai Hospital, Hatyai 90110, Songkhla, Thailand
| | - Arunchai Chang
- Division of Gastroenterology, Department of Internal Medicine, Hatyai Hospital, Hatyai 90110, Songkhla, Thailand
| | | | | | - Keerati Akarapatima
- Division of Gastroenterology, Department of Internal Medicine, Hatyai Hospital, Hatyai 90110, Songkhla, Thailand
| | - Apiradee Songjamrat
- Division of Intervention Radiology, Department of Radiology, Hatyai Hospital, Hatyai 90110, Songkhla, Thailand
| | - Songklod Pakdeejit
- Division of Intervention Radiology, Department of Radiology, Hatyai Hospital, Hatyai 90110, Songkhla, Thailand
| | - Varayu Prachayakul
- Siriraj Gastrointestinal Endoscopy Center, Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkoknoi 10700, Bangkok, Thailand
| | - Teerha Piratvisuth
- NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Faculty of Medicine, Prince of Songkla University, Hatyai 90110, Songkhla, Thailand
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Mechanisms of chronic alcohol exposure-induced aggressiveness in cellular model of HCC and recovery after alcohol withdrawal. Cell Mol Life Sci 2022; 79:366. [PMID: 35713728 PMCID: PMC9205837 DOI: 10.1007/s00018-022-04387-y] [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] [Received: 10/30/2021] [Revised: 04/28/2022] [Accepted: 05/20/2022] [Indexed: 11/27/2022]
Abstract
Alcohol-related liver disease is the most prevalent chronic liver disease worldwide, accounting for 30% of hepatocellular carcinoma (HCC) cases and HCC-specific deaths. However, the knowledge on mechanisms by which alcohol consumption leads to cancer progression and its aggressiveness is limited. Better understanding of the clinical features and the mechanisms of alcohol-induced HCC are of critical importance for prevention and the development of novel treatments. Early stage Huh-7 and advanced SNU449 liver cancer cell lines were subjected to chronic alcohol exposure (CAE), at different doses for 6 months followed by 1-month alcohol withdrawal period. ADH activity and ALDH expression were much lower in SNU449 compared with Huh-7 cells and at the 270 mM dose, CAE decreased cell viability by about 50% and 80%, respectively, in Huh-7 and SNU449 cells but induced mortality only in Huh-7 cells. Thus, Huh-7 may be more vulnerable to ethanol toxicity because of the higher levels of acetaldehyde. CAE induced a dose-dependent increase in cell migration and invasion and also in the expression of cancer stem cells markers (CD133, CD44, CD90). CAE in Huh-7 cells selectively activated ERK1/2 and inhibited GSK3β signaling pathways. Most of the changes induced by CAE were reversed after alcohol withdrawal. Interestingly, we confirmed the increase in CD133 mRNA levels in the tumoral tissue of patients with ethanol-related HCC compared to other HCC etiologies. Our results may explain the benefits observed in epidemiological studies showing a significant increase of overall survival in abstinent compared with non-abstinent patients.
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Trevisani F, Giannini EG. The ITA.LI.CA Consortium: How multicentre collaboration helped shape the management of patients with hepatocellular carcinoma on the basis of real-world evidence. Ann Hepatol 2022; 27 Suppl 1:100564. [PMID: 34688886 DOI: 10.1016/j.aohep.2021.100564] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 08/19/2021] [Indexed: 02/04/2023]
Abstract
The growing diffusion of digitalisation and informatics has promoted the creation and analysis of large databases able to provide solid information. Analyses of "big data" generated by real-world practice are particularly useful for knowing incidence and mortality, disparities, temporal trends of diseases, identifying risk factors, predicting future scenarios, obtaining inputs for cost-effectiveness and treatment benefit modelling, designing new studies, and monitoring rare diseases. Although randomised controlled trials (RCTs) represent the gold-standard for generating evidence about new diagnostic, preventive or therapeutic procedures, their results should be integrated with real-world data to personalise patient management. Indeed, a substantial proportion of patients observed in field-practice have characteristics that prevent the access to RCTs or, when included, form sub-groups too small to provide robust post-hoc analyses. Furthermore, as RCTs are resource-consuming and designed to maximize the probability of success, they are generally performed in expert centres of high-income areas, excluding economically-deprived regions which could complementarily contribute to the medical progress as huge sources of real-world data. These considerations fuelled the creation in 1998 of the Italian Liver Cancer (ITA.LI.CA) consortium, with the aim to merge data of patients with hepatocellular carcinoma (HCC) managed in several centres. This cooperation permitted to analyse a multicentre, large cohort of HCC patients. Since then, the ITA.LI.CA group has progressively expanded to currently include 24 centres, and its database counts more than 9,000 patients. This article describes the history of the ITA.LI.CA consortium and presents its scientific production whose results greatly contributed to the incessant improvement of HCC management.
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Affiliation(s)
- Franco Trevisani
- Medical Semeiotics Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Italy; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
| | - Edoardo G Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy
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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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Guo Y, Hu J, Zhao Z, Zhong G, Gong J, Cai D. Identification of a Prognostic Model Based on 2-Gene Signature and Analysis of Corresponding Tumor Microenvironment in Alcohol-Related Hepatocellular Carcinoma. Front Oncol 2021; 11:719355. [PMID: 34646769 PMCID: PMC8503534 DOI: 10.3389/fonc.2021.719355] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 09/10/2021] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors with the poor prognosis. Nowadays, alcohol is becoming a leading risk factor of HCC in many countries. In our study, we obtained the DEGs in alcohol-related HCC through two databases (TCGA and GEO). Subsequently, we performed enrichment analyses (GO and KEGG), constructed the PPI network and screened the 53 hub genes by Cytoscape. Two genes (BUB1B and CENPF) from hub genes was screened by LASSO and Cox regression analyses to construct the prognostic model. Then, we found that the high risk group had the worse prognosis and verified the clinical value of the risk score in alcohol-related HCC. Finally, we analyzed the tumor microenvironment between high and low risk groups through CIBERSORT and ESTIMATE. In summary, we constructed the two-gene prognostic model that could predict the poor prognosis in patients with alcohol-related HCC.
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Affiliation(s)
- Yong Guo
- Department of Hepatobiliary Surgery, People's Hospital of Changshou, Chongqing, China
| | - Jiejun Hu
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhibo Zhao
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Guochao Zhong
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jianping Gong
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Dong Cai
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Ganne-Carrié N, Nahon P, Chaffaut C, N’Kontchou G, Layese R, Audureau E, Chevret S. Impact of cirrhosis aetiology on incidence and prognosis of hepatocellular carcinoma diagnosed during surveillance. JHEP Rep 2021; 3:100285. [PMID: 34522876 PMCID: PMC8424277 DOI: 10.1016/j.jhepr.2021.100285] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Revised: 03/04/2021] [Accepted: 03/07/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND & AIMS In this study we aimed to analyse the impact of the aetiology of cirrhosis on the incidence, characteristics and prognosis of hepatocellular carcinoma (HCC) diagnosed during a surveillance program. METHODS Individual data from a randomized trial and 2 prospective cohorts of patients with compensated histologically proven cirrhosis recruited between 2000 and 2016 were pooled. The influence of cirrhosis aetiology on survival after HCC detection was assessed using multivariable regression models. RESULTS Among 3,533 patients (1,926 virus [VIR], 1,167 alcohol [ALC], 440 combined [MIX]), 431 were diagnosed with HCC after a median follow-up of 57.1 months. The 5-year HCC incidence was lowest in ALC (VIR 12.6%, ALC 9.1%, MIX 14.3%, p = 0.04). At the time of diagnosis, tumour burden and Child-Pugh score were comparable across aetiology groups, but early BCLC stages (0/A) were significantly less frequent in ALC (VIR 80%, ALC 37%, MIX 72%) as a result of worse ECOG performance status. However, similar access to first-line curative HCC treatment was reported across aetiology groups (p = 0.68). Median survival after HCC diagnosis was significantly reduced in ALC (VIR 39, ALC 21, MIX 34 months, p = 0.02). However, when adjusting for tumour size, ECOG and Child-Pugh score, the aetiology of the underlying cirrhosis no longer had a significant impact. CONCLUSION Compared to patients with virus-related cirrhosis, patients with alcohol-related compensated cirrhosis enrolled in a surveillance program have: i) the lowest 5-year HCC incidence; ii) worse overall prognosis, mostly driven by a poor general condition, despite similar access to first-line curative treatment. LAY SUMMARY It has been suggested that early detection of hepatocellular carcinoma (HCC) may be futile in patients with alcohol-related cirrhosis. By comparing outcomes in more than 3,000 patients with compensated cirrhosis included in surveillance programs, this study suggests that HCC surveillance enables early diagnosis in most patients with alcohol-related cirrhosis despite a higher competing risk of death in these patients. We also report similar access to first-line curative HCC treatment in these patients compared to those with viral cirrhosis, despite higher rates of comorbidities and impaired liver function. Following HCC detection, the later parameters were major drivers of death irrespective of the cause of cirrhosis. REGISTRATION CHC2000 (NCT00190385) and CIRRAL (NCT01213927) cohorts were registered at ClinicalTrials.gov and the full protocols are available at the following links (https://clinicaltrials.gov/ct2/show/NCT00190385) and https://clinicaltrials.gov/ct2/show/NCT01213927, respectively). The full CirVir protocol is available via the ANRS Web site (http://anrs.fr).
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Affiliation(s)
- Nathalie Ganne-Carrié
- AP-HP, Hôpitaux Universitaires Paris Seine Saint-Denis, APHP, Liver Unit, Bobigny, France
- Université Sorbonne Paris Nord, F-93000 Bobigny, France
- Inserm, UMR–1138 «Functional Genomics of solid tumors», Centre de recherche des Cordeliers, Université de Paris, France
| | - Pierre Nahon
- AP-HP, Hôpitaux Universitaires Paris Seine Saint-Denis, APHP, Liver Unit, Bobigny, France
- Université Sorbonne Paris Nord, F-93000 Bobigny, France
- Inserm, UMR–1138 «Functional Genomics of solid tumors», Centre de recherche des Cordeliers, Université de Paris, France
| | - Cendrine Chaffaut
- SBIM, APHP, Hôpital Saint-Louis, Paris, Inserm, UMR-1153, ECSTRA Team, Paris, France
| | - Gisèle N’Kontchou
- AP-HP, Hôpitaux Universitaires Paris Seine Saint-Denis, APHP, Liver Unit, Bobigny, France
| | - Richard Layese
- Santé publique, APHP, hôpital Henri Mondor; Clinical Epidemiology and Ageing EA7376 UPEC, Créteil, France
| | - Etienne Audureau
- Santé publique, APHP, hôpital Henri Mondor; Clinical Epidemiology and Ageing EA7376 UPEC, Créteil, France
| | - Sylvie Chevret
- SBIM, APHP, Hôpital Saint-Louis, Paris, Inserm, UMR-1153, ECSTRA Team, Paris, France
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Distinctive Features and Outcomes of Hepatocellular Carcinoma in Patients With Alcohol-Related Liver Disease: A US Multicenter Study. Clin Transl Gastroenterol 2021; 11:e00139. [PMID: 32352723 PMCID: PMC7145044 DOI: 10.14309/ctg.0000000000000139] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The burden of hepatocellular carcinoma (HCC) occurring in patients with alcoholic liver disease (ALD) is increasing at an alarming rate. The aims of this study were to compare the patient and tumor characteristics of HCC occurring in ALD-alone relative to and in addition to other chronic liver diseases.
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Buchanan R, Sinclair JMA. Alcohol use disorder and the liver. Addiction 2021; 116:1270-1278. [PMID: 32710592 DOI: 10.1111/add.15204] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 06/19/2020] [Accepted: 07/17/2020] [Indexed: 12/23/2022]
Abstract
Alcohol use disorders (AUD) cause a range of physical harms, but the major cause of alcohol-related mortality is alcohol-related liver disease (ALD), in some countries accounting for almost 90% of alcohol-related deaths. The risk of ALD has an exponential relationship with increasing alcohol consumption, but is also associated with genetic factors, other life-style factors and social deprivation. ALD includes a spectrum of progressive pathology, from liver steatosis to fibrosis and liver cirrhosis. There are no specific treatments for liver cirrhosis, but abstinence from alcohol is key to limit progression of the disease. Over time, cirrhosis can progress (often silently) to decompensated cirrhosis and hepatocellular carcinoma (HCC). Liver transplantation may be suitable for patients with decompensated liver cirrhosis and may also be used as a curative intervention for HCC, but only for a few selected patients, and complete abstinence is a prerequisite. Patients with AUD are also at risk of developing alcoholic hepatitis, which has a high mortality and limited evidence for effective therapies. There is a strong evidence base for the effectiveness of psychosocial and pharmacological interventions for AUD, but very few of these have been trialled in patients with comorbid ALD. Integrated specialist alcohol and hepatology collaborations are required to develop interventions and pathways for patients with ALD and ongoing AUD.
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Affiliation(s)
- Ryan Buchanan
- Department of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Julia M A Sinclair
- Department of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
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38
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Garuti F, Neri A, Avanzato F, Gramenzi A, Rampoldi D, Rucci P, Farinati F, Giannini EG, Piscaglia F, Rapaccini GL, Di Marco M, Caturelli E, Zoli M, Sacco R, Cabibbo G, Marra F, Mega A, Morisco F, Gasbarrini A, Svegliati-Baroni G, Foschi FG, Missale G, Masotto A, Nardone G, Raimondo G, Azzaroli F, Vidili G, Brunetto MR, Trevisani F. The changing scenario of hepatocellular carcinoma in Italy: an update. Liver Int 2021; 41:585-597. [PMID: 33219585 DOI: 10.1111/liv.14735] [Citation(s) in RCA: 73] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 10/26/2020] [Accepted: 11/13/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIMS Epidemiology of hepatocellular carcinoma (HCC) is changing in most areas of the world. This study aimed at updating the changing scenario of aetiology, clinical presentation, management and prognosis of HCC in Italy during the last 15 years. METHODS Retrospective analysis of the Italian Liver Cancer (ITA.LI.CA) database included 6034 HCC patients managed in 23 centres from 2004 to 2018. Patients were divided into three groups according to the date of cancer diagnosis (2004-2008, 2009-2013 and 2014-2018). RESULTS The main results were: (i) a progressive patient ageing; (ii) a progressive increase of non-viral cases and, particularly, of 'metabolic' and 'metabolic + alcohol' HCCs; (iii) a slightly decline of cases diagnosed under surveillance, but with an incremental use of the semiannual schedule; (iv) a favourable cancer stage migration; (v) an increased use of radiofrequency ablation to the detriment of percutaneous ethanol injection; (vi) improved outcomes of ablative and transarterial treatments; (vii) an improved overall survival (adjusted for the lead time in surveyed patients) in the last calendar period, particularly in viral patients; (viii) a large gap between the number of potential candidates (according to oncologic criteria and age) to liver transplant and that of transplanted patients. CONCLUSIONS During the last 15 years several aspects of HCC scenario have changed, as well as its management. The improvement in patient survival observed in the last period was likely because of a larger use of thermal ablation with respect to the less effective alcohol injection and to an improved management of intermediate stage patients.
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Affiliation(s)
- Francesca Garuti
- Semeiotics Unit, Department of Medical and Surgical Sciences, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Andrea Neri
- Semeiotics Unit, Department of Medical and Surgical Sciences, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Francesca Avanzato
- Semeiotics Unit, Department of Medical and Surgical Sciences, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Annagiulia Gramenzi
- Semeiotics Unit, Department of Medical and Surgical Sciences, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Davide Rampoldi
- Semeiotics Unit, Department of Medical and Surgical Sciences, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Paola Rucci
- Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Edoardo G Giannini
- Department of Internal Medicine, Gastroenterology Unit, University of Genova, IRCCS Policlinico San Martino, Genova, Italy
| | - Fabio Piscaglia
- Internal Medicine-Piscaglia Unit, Department of Medical and Surgical Sciences, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | | | | | | | - Marco Zoli
- Internal Medicine-Zoli Unit, Department of Medical and Surgical Sciences, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Rodolfo Sacco
- Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, Foggia, Italy
| | - Giuseppe Cabibbo
- Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy
| | - Fabio Marra
- Department of Experimental and Clinical Medicine, Internal Medicine and Hepatology Unit, University of Firenze, Firenze, Italy
| | - Andrea Mega
- Gastroenterology Unit, Bolzano Regional Hospital, Bolzano, Italy
| | - Filomena Morisco
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Napoli "Federico II", Napoli, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology Unit, Policlinico Gemelli, Università Cattolica del Sacro Cuore, Roma, Italy
| | | | - Francesco G Foschi
- Department of Internal Medicine, Ospedale per gli Infermi of Faenza, Faenza, Italy
| | - Gabriele Missale
- Infectious Diseases and Hepatology Unit, Azienda Ospedaliero-Universitaria of Parma, Parma, Italy
| | - Alberto Masotto
- Gastroenterology Unit, Ospedale Sacro Cuore Don Calabria, Negrar, Italy
| | - Gerardo Nardone
- Department of Clinical Medicine and Surgery, Hepato-Gastroenterology Unit, University of Napoli "Federico II", Napoli, Italy
| | - Giovanni Raimondo
- Department of Clinical and Experimental Medicine, Clinical and Molecular Hepatology Unit, University of Messina, Messina, Italy
| | - Francesco Azzaroli
- Gastroenterology Unit, Department of Surgical and Medical Sciences, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Gianpaolo Vidili
- Department of Medical, Surgical and Experimental Sciences, Clinica Medica Unit, University of Sassari, Azienda Ospedaliero-Universitaria of Sassari, Sassari, Italy
| | - Maurizia R Brunetto
- Hepatology and Liver Physiopathology Laboratory and Internal Medicine, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Franco Trevisani
- Semeiotics Unit, Department of Medical and Surgical Sciences, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
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Hsieh MH, Kao TY, Hsieh TH, Kao CC, Peng CY, Lai HC, Chuang PH, Kao JT. Prognostic roles of diabetes mellitus and hypertension in advanced hepatocellular carcinoma treated with sorafenib. PLoS One 2021; 15:e0244293. [PMID: 33382703 PMCID: PMC7775090 DOI: 10.1371/journal.pone.0244293] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Accepted: 12/08/2020] [Indexed: 12/09/2022] Open
Abstract
BACKGROUND & AIMS It remains limited whether diabetes mellitus (DM) and hypertension (HTN) affect the prognosis of advanced hepatocellular carcinoma (HCC) treated with sorafenib. Our study attempted to elucidate the roles of DM/HTN and the effects of diabetes medications among advanced HCC patients receiving sorafenib. METHODS From August 2012 to February 2018, 733 advanced HCC patients receiving sorafenib were enrolled at China Medical University, Taichung, Taiwan. According to the presence/absence of DM or HTN, they were divided into four groups: control [DM(-)/HTN(-), n = 353], DM-only [DM(+)/HTN(-), n = 91], HTN-only [DM(-)/HTN(+), n = 184] and DM+HTN groups [DM(+)/HTN(+), n = 105]. Based on the types of diabetes medications, there were three groups among DM patients (the combined cohort of DM-only and DM+HTN groups), including metformin (n = 63), non-metformin oral hypoglycemic agent (OHA) (n = 104) and regular insulin (RI)/neutral protamine hagedorn (NPH) groups (n = 29). We then assessed the survival differences between these groups. RESULTS DM-only and DM+HTN groups significantly presented longer overall survival (OS) than control group (control vs. DM-only, 7.70 vs. 11.83 months, p = 0.003; control vs. DM+HTN, 7.70 vs. 11.43 months, p = 0.008). However, there was no significant OS difference between control and HTN-only group (7.70 vs. 8.80 months, p = 0.111). Besides, all groups of DM patients showed significantly longer OS than control group (control vs. metformin, 7.70 vs. 12.60 months, p = 0.011; control vs. non-metformin OHA, 7.70 vs. 10.80 months, p = 0.016; control vs. RI/NPH, 7.70 vs. 15.20 months, p = 0.026). CONCLUSIONS Rather than HTN, DM predicts better prognosis in advanced HCC treated with sorafenib. Besides, metformin, non-metformin OHA and RI/NPH are associated with longer survival among DM-related advanced HCC patients receiving sorafenib.
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Affiliation(s)
- Ming-Han Hsieh
- Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Tzu-Yu Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Ting-Hui Hsieh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chun-Chi Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Cheng-Yuan Peng
- Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Hsueh-Chou Lai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Po-Heng Chuang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Jung-Ta Kao
- Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- * E-mail:
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Zhang W, Liu F, Huang J, Guo X, Dong W, Wei S, Li L, Zhu X, Zhou W, Liu H. Effect of menopausal status on the survival and recurrence of sex-classified hepatocellular carcinoma after liver resection: a case-matched study with propensity score matching. Aging (Albany NY) 2020; 12:25895-25915. [PMID: 33232278 PMCID: PMC7803575 DOI: 10.18632/aging.202155] [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: 02/24/2020] [Accepted: 09/24/2020] [Indexed: 12/29/2022]
Abstract
OBJECTIVE To investigate the impact of menopausal status on the prognosis for sex-classified Hepatocellular carcinoma (HCC) and to establish prognostic nomograms for patients after liver resection. RESULTS After propensity score matching (PSM), statistically significant differences in both overall survival (OS) and recurrence-free survival (RFS) were found between men and women HCC patients. Based on Cox regression analysis, these differences were evident in the normal menstruation (N) group expanded with male patients, but not in either the expanded postmenopausal (P) or intermediate (I) groups. Sex disparity was also apparent in the recurrence-free survival (RFS) of the total HCC patients. Integrated with independent factors, nomograms for the OS and RFS of the expanded N group showed higher C-indices of 0.773 and 0.724, respectively, than those of nomograms for the total patients and BCLC stage (P<0.001). CONCLUSION Sex disparity appears to affect both the survival and recurrence of HCC only in normal menstruation women and their matched men. For predicting survival, prognostic nomograms derived from the expanded N group of HCC patients were more accurate for patients with the same clinical conditions. METHODS The patients (390 females and 1920 males), who underwent curative liver resection for HCC during 2008 to 2012, were screened. The 390 women were divided into three groups: normal menstruation, intermediate, and postmenopausal. To overcome selection bias, the three groups of females were matched with males at a ratio of 1:2, using propensity score matching. Based on further Cox regression analysis, independent factors were integrated into nomograms for OS and RFS by R rms. The accuracy and discrimination of the nomograms were evaluated by the C-index, calibration curve, and decision curve analysis.
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Affiliation(s)
- Wenli Zhang
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
| | - Fuchen Liu
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
| | - Jian Huang
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
| | - Xinggang Guo
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.,Changhai Hospital, Second Military Medical University, Shanghai 200438, China
| | - Wei Dong
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
| | - Shuxun Wei
- The First Department of General Surgery, Changzheng Hospital, Second Military Medical University and Naval Medical University, Shanghai 200438, China
| | - Li Li
- Department of Nephrology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Xiuli Zhu
- Department of Gastroenterology, Anhui Provincial Hospital, University of Science and Technology of China, Hefei, Anhui, China
| | - Weiping Zhou
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
| | - Hui Liu
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
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Mehta R, Tang Qinghe, Tsilimigras DI, Paredes A, Dillhoff M, Cloyd JM, Ejaz A, Tsung A, Spolverato G, Pawlik TM. Long-term outcomes after resection of alcohol-related versus hepatitis-related hepatocellular carcinoma: A SEER-Medicare database analysis. Am J Surg 2020; 222:167-172. [PMID: 33131693 DOI: 10.1016/j.amjsurg.2020.10.033] [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: 06/01/2020] [Revised: 09/15/2020] [Accepted: 10/23/2020] [Indexed: 11/15/2022]
Abstract
BACKGROUND The objective of this study was to define the relative impact of alcohol and/or hepatitis-related HCC etiology on the outcomes of patients who underwent resection or transplantation for HCC. METHODS The SEER-Medicare database was used to identify patients with HCC between 2004 and 2015. Patients with history of alcohol abuse or hepatitis were identified. Overall survival (OS) and cancer-specific survival (CSS) were calculated using the Kaplan-Meier method and multivariable Cox regression analysis. RESULTS Among 1140 patients, 11.9% (n = 136) of patients had alcohol-related HCC, 30.0% (n = 342) hepatitis-related HCC, and 58.1% (n = 662) had other cause-related HCC. On multivariable analysis, patients with alcohol-related HCC (HR:1.06, 95%CI:0.82-1.35) or hepatitis-related HCC (HR:1.05, 95%CI:0.88-1.26) had similar hazards of death compared with patients who had non-alcohol/non-hepatitis-related HCC. Patients who had tumor size ≤5 cm had lower hazards of death (HR:0.81, 95%CI:0.68-0.97), while individuals who underwent liver resection (vs. transplantation) had almost a two-fold higher hazards of death (HR:1.99, 95%CI:1.47-2.69). CONCLUSION Tumor specific factors (i.e. tumor size and stage) and operative approach (i.e. resection vs. transplantation) -rather than HCC etiology- dictated both OS and CSS.
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Affiliation(s)
- Rittal Mehta
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Tang Qinghe
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Hepatobiliary and Pancreatic Surgery, Shanghai East Hospital, Tongji University, Shanghai, China
| | | | - Anghela Paredes
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Mary Dillhoff
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Jordan M Cloyd
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Aslam Ejaz
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Allan Tsung
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Gaya Spolverato
- Department of Surgical, Gastroenterological and Oncological Sciences, University of Padova, Italy
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
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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: 107] [Impact Index Per Article: 21.4] [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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Luo Y, Ye J, Wei J, Zhang J, Li Y. Long non‑coding RNA‑based risk scoring system predicts prognosis of alcohol‑related hepatocellular carcinoma. Mol Med Rep 2020; 22:997-1007. [PMID: 32468063 PMCID: PMC7339747 DOI: 10.3892/mmr.2020.11179] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Accepted: 04/22/2020] [Indexed: 12/16/2022] Open
Abstract
Increasing evidence suggests that long non-coding RNAs (lncRNAs) serve a crucial role in predicting prognosis for hepatocellular carcinoma (HCC). However, prognostic performance may not be the same for alcohol‑related HCC. The aim of the present study was to screen prognosis‑associated lncRNAs and construct a risk scoring system for alcohol‑related HCC. The expression profiles of lncRNAs in 113 patients with alcohol‑related HCC and 224 with non‑alcohol‑related HCC were obtained from The Cancer Genome Atlas (TCGA) database and screened for differentially expressed lncRNAs. Cox regression analysis was performed to identify prognosis‑associated lncRNAs and select the optimal lncRNA model. A risk scoring system was established to calculate the risk score for each patient. The prognostic ability of this system was tested. Functional enrichment analysis was performed for genes that were highly associated with lncRNA expression. A total of 102 differentially expressed lncRNAs were identified between alcohol‑related and non‑alcohol‑related HCC. Four lncRNAs (AC012640.1, AC013451.2, AC062004.1 and LINC02334) were used to construct the risk assessment model to predict overall survival (OS), and five lncRNAs (ERVH48‑1, LINC02043, LINC01605, AC062004.1 and AL139385) were used to predict recurrence‑free survival (RFS). Patients were assigned to high‑ or low‑risk groups according to the risk score. OS in the high‑risk group was significantly shorter than that of the low‑risk group. The area under the receiver operating characteristic (ROC) curve of risk scoring systems was >0.7. The risk score was an independent prognostic factor for alcohol‑related HCC. Functional enrichment analysis demonstrated that lncRNA‑related genes found in this system were mainly involved in chemical carcinogenesis, drug metabolism, and the cell cycle. In conclusion, this study developed and validated a prognostic scoring system for alcohol‑related HCC based on lncRNAs.
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Affiliation(s)
- Yue Luo
- Department of Medical Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Jiaxiang Ye
- Department of Medical Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Jiazhang Wei
- Department of Otolaryngology and Head and Neck, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China
| | - Jinyan Zhang
- Department of Medical Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Yongqiang Li
- Department of Medical Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
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Alcohol-related liver disease: Clinical practice guidelines by the Latin American Association for the Study of the Liver (ALEH). Ann Hepatol 2020; 18:518-535. [PMID: 31053546 DOI: 10.1016/j.aohep.2019.04.005] [Citation(s) in RCA: 76] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Accepted: 03/06/2019] [Indexed: 02/04/2023]
Abstract
Alcohol-related liver disease (ALD) is a major cause of advanced chronic liver disease in Latin-America, although data on prevalence is limited. Public health policies aimed at reducing the alarming prevalence of alcohol use disorder in Latin-America should be implemented. ALD comprises a clinical-pathological spectrum that ranges from steatosis, steatohepatitis to advanced forms such as alcoholic hepatitis (AH), cirrhosis and hepatocellular carcinoma. Besides genetic factors, the amount of alcohol consumption is the most important risk factor for the development of ALD. Continuous consumption of more than 3 standard drinks per day in men and more than 2 drinks per day in women increases the risk of developing liver disease. The pathogenesis of ALD is only partially understood and recent translational studies have identified novel therapeutic targets. Early forms of ALD are often missed and most clinical attention is focused on AH, which is defined as an abrupt onset of jaundice and liver-related complications. In patients with potential confounding factors, a transjugular biopsy is recommended. The standard therapy for AH (i.e. prednisolone) has not evolved in the last decades yet promising new therapies (i.e. G-CSF, N-acetylcysteine) have been recently proposed. In both patients with early and severe ALD, prolonged abstinence is the most efficient therapeutic measure to decrease long-term morbidity and mortality. A multidisciplinary team including alcohol addiction specialists is recommended to manage patients with ALD. Liver transplantation should be considered in the management of patients with end-stage ALD that do not recover despite abstinence. In selected cases, increasing number of centers are proposing early transplantation for patients with severe AH not responding to medical therapy.
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Brancaccio G, Vitale A, Signoriello G, Gaeta GB, Cillo U. Changing indications for liver transplant: slow decline of hepatitis viruses in Italy. Infect Dis (Lond) 2020; 52:557-562. [PMID: 32401092 DOI: 10.1080/23744235.2020.1763453] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Background: The indications to LT are changing rapidly in Europe and the U.S. mainly due to the extensive use of direct-acting antiviral agents (DAA) against HCV. Italy was an endemic area for viral hepatitis.Methods: The study reviewed liver transplant registry of a leading Italian centre from the year 2014 (the year before the extensive use of DAA in Italy) to December 2018, with the scope of recording trends in indications. The indications were categorised as: HCV; HBV ± HDV; alcohol-dependent liver disease (ALD); NASH; mescellaneous. Transplants for decompensation or hepatocellular carcinoma were analysed separately. The data were analysed using standard statistical methods.Results: During the study period 463 LTs were accomplished. For the scope of the present study second transplants and transplant in patients <18 years were eliminated; in all, 397 patients were analysed. Overall, HCV infection was the main aetiological factor leading to transplant (139/397, 35%) followed by alcohol use (20.9%), HBV ± HDV (15.8%) and NASH (12.8%). In the decompensation group HCV decreased from 41.9% in 2014 to 14.3% in 2018 while alcohol increased (p < .001); in the HCC group, HCV decreased from 52.6% to 34% and alcohol and NASH increased; the number and proportion of HBV infections remained stable over time, with a 56% prevalence of HDV among decompensated patients.Conclusion: LT landscape is rapidly evolving; hepatitis virus infections still maintain a remarkable proportion among the indications for LT in an area that reached in the past high endemic levels for hepatitis C and B.
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Affiliation(s)
| | - Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy
| | - Giuseppe Signoriello
- Biostatistics, Department of Mental and Physical Health and Preventive Medicine, Campania University L. Vanvitelli, Naples, Italy
| | - Giovanni B Gaeta
- Infectious Diseases, Department of Mental and Physical Health and Preventive Medicine, Campania University L. Vanvitelli, Naples, Italy
| | - Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy
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Kim HY, Dufour JF. Intricate interpretation of etiology-specific outcome comparison in patients with hepatocellular carcinoma. Clin Mol Hepatol 2020; 26:238-239. [PMID: 32178487 PMCID: PMC7160345 DOI: 10.3350/cmh.2020.0051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2020] [Accepted: 03/09/2020] [Indexed: 11/06/2022] Open
Affiliation(s)
- Hwi Young Kim
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
| | - Jean-François Dufour
- Hepatology, Department of Clinical Research, University of Bern, Bern, Switzerland
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The Changing Epidemiology of Hepatocellular Carcinoma : Experience of a Single Center. BIOMED RESEARCH INTERNATIONAL 2020; 2020:5309307. [PMID: 32185209 PMCID: PMC7063180 DOI: 10.1155/2020/5309307] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Accepted: 01/27/2020] [Indexed: 02/08/2023]
Abstract
Aims To analyze the main etiological factors and some clinical features of patients with hepatocellular carcinoma (HCC) at diagnosis and to compare them with those we described ten years ago. Materials and Methods. We compared two groups of patients with HCC, Group 1 consisting of 132 patients (82 M, 50 F) diagnosed in the 2003–2008 period and Group 2 including 119 patients (82 M, 37 F) diagnosed in the 2013–2018 period. For all patients, age, sex, viral markers, alcohol consumption, serum alpha-fetoprotein (AFP) levels, and the main liver function parameters were recorded. The diagnosis of HCC was based on AASLD, EASL guidelines. The staging was classified according to the “Barcelona Clinic Liver Cancer staging system” (BCLC). Results Mean age was 69.0 ± 8 years in Group 1 and 71.0 ± 9 in Group 2 (P < 0.05). HCV subjects were significantly older in Group 2 (P < 0.05). HCV subjects were significantly older in Group 2 (P < 0.05). HCV subjects were significantly older in Group 2 (P < 0.05). HCV subjects were significantly older in Group 2 (P < 0.05). HCV subjects were significantly older in Group 2 (P < 0.05). HCV subjects were significantly older in Group 2 (P < 0.05). HCV subjects were significantly older in Group 2 (P < 0.05). HCV subjects were significantly older in Group 2 ( Conclusions This study shows that over the last decade a number of features of patients with HCC in our region have changed, particularly age at onset, etiological factors, and staging of HCC.
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Costentin CE, Sogni P, Falissard B, Barbare JC, Bendersky N, Farges O, Goutte N. Geographical Disparities of Outcomes of Hepatocellular Carcinoma in France: The Heavier Burden of Alcohol Compared to Hepatitis C. Dig Dis Sci 2020; 65:301-311. [PMID: 31346950 DOI: 10.1007/s10620-019-05724-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 07/03/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Data on alcohol-related HCC are limited. AIMS Our aim was to describe the incidence, management, and prognosis of alcohol compared to Hepatitis C (HCV)-related HCC at a national level. METHODS Incident cases of HCC were identified in French healthcare databases between 2009 and 2012 and analyzed retrospectively. Demographic data, type, location, and annual HCC-caseload of the hospitals where patients were first managed were retrieved. Survival of incident cases was computed from the time of diagnosis and adjusted for potential confounding variables. RESULTS The study population included 14,060 incident cases of alcohol and 2581 HCV-related HCC. Alcohol-related HCC was more frequent than HCV-related HCC (29.37 and 5.39/100,000 adults/year, respectively) with an heterogeneous distribution on the French territory. The optimal treatment was less frequently curative (20.5% vs 35.9%; p < 0.001), and survival was significantly shorter (9.5 [9.0-10.0] versus 16.8 [15.5-18.7] months p < 0.001) in alcohol compared to HCV-related HCC, with marked variations between regions for a given risk factor. In multivariable analysis in the whole study population, curative treatment was a strong predictor of survival (adjusted HR 0.28 [0.27-0.30] months p < 0.001). Being managed at least once in a teaching hospital during follow-up was independently associated with receiving a curative treatment and survival. CONCLUSION In France, incidence of alcohol-related HCC is high and prognosis is poor compared to HCV-related HCC, with marked variations between regions. These results should guide future health policy initiatives pertaining to HCC care. Importantly, increasing patient' referral in expert centers could increase chances to receive curative treatment and improve outcomes.
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Affiliation(s)
- Charlotte E Costentin
- Clinique Universitaire d'Hépato-gastroentérologie, Pôle Digidune, University Hospital Grenoble Alpes, La Tronche, France. .,Grenoble Alpes University, Inserm U1041, Grenoble, France.
| | - Philippe Sogni
- INSERM U-1223, Pasteur Institute, Paris and Hepatology, Cochin Hospital, Assistance Publique - Hopitaux de Paris, France, Paris-Descartes University, Paris, France
| | | | - Jean-Claude Barbare
- Amiens University Hospital, délégation à la recherche clinique et à l'innovation, site sud, 80054, Amiens, France
| | | | - Olivier Farges
- Hepato-biliary Surgery, Beaujon Hospital, Clichy, France
| | - Nathalie Goutte
- Paris XI University, INSERM UMRS-1193, DHU Hépatinov and Centre hépatobiliaire, Paul-Brousse Hospital, Assistance Publique - Hôpitaux de Paris, Villejuif, France
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Nilsson E, Anderson H, Sargenti K, Lindgren S, Prytz H. Risk and outcome of hepatocellular carcinoma in liver cirrhosis in Southern Sweden: a population-based study. Scand J Gastroenterol 2019; 54:1027-1032. [PMID: 31389730 DOI: 10.1080/00365521.2019.1649454] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Background and aims: Liver cirrhosis is a risk factor for hepatocellular carcinoma (HCC). While the HCC risk is thought to be highest in hepatitis B and hepatitis C, the risk in other cirrhosis etiologies is not fully established. Therefore, we aimed to study the risk and outcome of HCC in alcoholic cirrhosis compared to cirrhosis of other etiologies, in Sweden. Material and methods: We used population-based medical registries to identify patients diagnosed with cirrhosis in the Scania region in southern Sweden between 2001 and 2010. Medical records were reviewed to identify all HCC cases and to register clinical parameters. All patients were followed until death, emigration or December 2017. Results: The cohort comprised 1317 patients with cirrhosis. A total of 200 patient developed HCC, including 75 with prevalent HCC. The annual incidence of HCC after six months was 1.5% in alcoholic cirrhosis and 4.7% in hepatitis C cirrhosis. In alcoholic cirrhosis, 40 patients were diagnosed with HCC during follow-up, of which 15 patients fulfilled the Milan criteria and 10 received treatment, curative or palliative. The overall median survival after HCC diagnosis was 7.7 months, with 4.5, 11 and 9.3 months, in cirrhosis due to alcohol, hepatitis C or remaining causes, respectively. Conclusion: We find an annual incidence of HCC in alcoholic cirrhosis of 1.5% indicating need for surveillance in these patients. Survival after HCC diagnosis was worst in alcoholic cirrhosis due to more advanced stage at diagnosis with few patients eligible for treatment.
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Affiliation(s)
- Emma Nilsson
- Department of Clinical Sciences, Lund University , Lund , Sweden.,Gastroenterology Clinic, Skåne University Hospital, Lund University , Lund , Sweden
| | - Harald Anderson
- Department of Clinical Sciences, Cancer Epidemiology, Lund University, Lund , Sweden
| | - Konstantina Sargenti
- Department of Clinical Sciences, Lund University , Lund , Sweden.,Gastroenterology Clinic, Skåne University Hospital, Lund University , Lund , Sweden
| | - Stefan Lindgren
- Gastroenterology Clinic, Skåne University Hospital, Lund University , Lund , Sweden.,Department of Clinical Sciences, Lund University , Malmö , Sweden
| | - Hanne Prytz
- Department of Clinical Sciences, Lund University , Lund , Sweden.,Gastroenterology Clinic, Skåne University Hospital, Lund University , Lund , Sweden
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Zhang X, Kang C, Li N, Liu X, Zhang J, Gao F, Dai L. Identification of special key genes for alcohol-related hepatocellular carcinoma through bioinformatic analysis. PeerJ 2019; 7:e6375. [PMID: 30755830 PMCID: PMC6368834 DOI: 10.7717/peerj.6375] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Accepted: 12/31/2018] [Indexed: 02/06/2023] Open
Abstract
Background Alcohol-related hepatocellular carcinoma (HCC) was reported to be diagnosed at a later stage, but the mechanism was unknown. This study aimed to identify special key genes (SKGs) during alcohol-related HCC development and progression. Methods The mRNA data of 369 HCC patients and the clinical information were downloaded from the Cancer Genome Atlas project (TCGA). The 310 patients with certain HCC-related risk factors were included for analysis and divided into seven groups according to the risk factors. Survival analyses were applied for the HCC patients of different groups. The patients with hepatitis B virus or hepatitis C virus infection only were combined into the HCC-V group for further analysis. The differentially expressed genes (DEGs) between the HCCs with alcohol consumption only (HCC-A) and HCC-V tumors were identified through limma package in R with cutoff criteria│log2 fold change (logFC)|>1.0 and p < 0.05. The DEGs between eight alcohol-related HCCs and their paired normal livers of GSE59259 from the Gene Expression Omnibus (GEO) were identified through GEO2R (a built-in tool in GEO database) with cutoff criteria |logFC|> 2.0 and adj.p < 0.05. The intersection of the two sets of DEGs was considered SKGs which were then investigated for their specificity through comparisons between HCC-A and other four HCC groups. The SKGs were analyzed for their correlations with HCC-A stage and grade and their prognostic power for HCC-A patients. The expressional differences of the SKGs in the HCCs in whole were also investigated through Gene Expression Profiling Interactive Analysis (GEPIA). The SKGs in HCC were validated through Oncomine database analysis. Results Pathological stage is an independent prognostic factor for HCC patients. HCC-A patients were diagnosed later than HCC patients with other risk factors. Ten SKGs were identified and nine of them were confirmed for their differences in paired samples of HCC-A patients. Three (SLC22A10, CD5L, and UROC1) and four (SLC22A10, UROC1, CSAG3, and CSMD1) confirmed genes were correlated with HCC-A stage and grade, respectively. SPP2 had a lower trend in HCC-A tumors and was negatively correlated with HCC-A stage and grade. The SKGs each was differentially expressed between HCC-A and at least one of other HCC groups. CD5L was identified to be favorable prognostic factor for overall survival while CSMD1 unfavorable prognostic factor for disease-free survival for HCC-A patients and HCC patients in whole. Through Oncomine database, the dysregulations of the SKGs in HCC and their clinical significance were confirmed. Conclusion The poor prognosis of HCC-A patients might be due to their later diagnosis. The SKGs, especially the four stage-correlated genes (CD5L, SLC22A10, UROC1, and SPP2) might play important roles in HCC development, especially alcohol-related HCC development and progression. CD5L might be useful for overall survival and CSMD1 for disease-free survival predication in HCC, especially alcohol-related HCC.
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Affiliation(s)
| | | | | | - Xiaoli Liu
- Henan Province People's Hospital, Zhengzhou, China
| | | | | | - Liping Dai
- Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
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