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Carbone M, Gerussi A, Cardinale V, Cazzagon N, Cossiga V, Lleo A, Marrone G, Marzioni M, Moschetta A, Muratori L, Rigamonti C, Vespasiani-Gentilucci U, Fraquelli M, Calvaruso V. Position paper of the Italian Association for the Study of the Liver (AISF): Management and treatment of primary biliary cholangitis. Dig Liver Dis 2024; 56:1461-1474. [PMID: 38902184 DOI: 10.1016/j.dld.2024.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 04/26/2024] [Accepted: 05/02/2024] [Indexed: 06/22/2024]
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Peng W, Xu B, Zhou H, Du J, Ge X, Huang S. Causal effects of autoimmune diseases on thyroid cancer: a two-sample Mendelian randomization study. Front Endocrinol (Lausanne) 2024; 15:1401458. [PMID: 39175579 PMCID: PMC11339619 DOI: 10.3389/fendo.2024.1401458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 07/18/2024] [Indexed: 08/24/2024] Open
Abstract
Background Although numerous studies had revealed associations between autoimmune diseases (AIDs) and thyroid cancer (TC), the potential causal associations between the two remain poorly defined. Methods Using five approaches, two-sample Mendelian randomization (MR) analyses were carried out to determine the causal effects of 12 major AIDs on risk of TC. The sensitivity analyses were conducted to verify the reliability of the analysis. The reverse MR analysis was performed to evaluate the possibility of reverse causation. Results The results showed a significant causal association of systemic lupus erythematosus (SLE) and primary biliary cirrhosis (PBC) on the risk of TC. Genetically predicted PBC elevated the risk of TC (OR = 1.46, 95% CI = 1.06-2.02, p = 0.021). The risk of TC was also increased by genetically predicted SLE (OR = 6.52, 95% CI = 1.38-30.84, p = 0.018) with heterogeneity. After outlier-corrected analyses, the results still suggested that genetically predicted SLE increased the risk of TC (p = 0.019). No evidence of a causal relationship between the remaining 10 AIDs and TC was observed. No reverse causal effects of TC on AIDs were found in reverse MR analysis. Conclusion These findings support a significant causal association of SLE/PBC on the increased risk of TC, indicating that patients with SLE/PBC should be under a close monitoring of TC.
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Affiliation(s)
| | | | | | | | | | - Shan Huang
- Department of Endocrinology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Zou Y, Zhu J, Song C, Li T, Wang K, Shi J, Ye H, Wang P. A polygenetic risk score combined with environmental factors better predict susceptibility to hepatocellular carcinoma in Chinese population. Cancer Med 2024; 13:e7230. [PMID: 38698686 PMCID: PMC11066500 DOI: 10.1002/cam4.7230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 04/11/2024] [Accepted: 04/18/2024] [Indexed: 05/05/2024] Open
Abstract
AIMS This study aimed to investigate environmental factors and genetic variant loci associated with hepatocellular carcinoma (HCC) in Chinese population and construct a weighted genetic risk score (wGRS) and polygenic risk score (PRS). METHODS A case-control study was applied to confirm the single nucleotide polymorphisms (SNPs) and environmental variables linked to HCC in the Chinese population, which had been screened by meta-analyses. wGRS and PRS were built in training sets and validation sets. Area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), Akaike information criterion (AIC), and Bayesian information criterion (BIC) were applied to evaluate the performance of the models. RESULTS A total of 13 SNPs were included in both risk prediction models. Compared with wGRS, PRS had better accuracy and discrimination ability in predicting HCC risk. The AUC for PRS in combination with drinking history, cirrhosis, HBV infection, and family history of HCC in training sets and validation sets (AUC: 0.86, 95% CI: 0.84-0.89; AUC: 0.85, 95% CI: 0.81-0.89) increased at least 20% than the AUC for PRS alone (AUC: 0.63, 95% CI: 0.60-0.67; AUC: 0.65, 95% CI: 0.60-0.71). CONCLUSIONS A novel model combining PRS with alcohol history, HBV infection, cirrhosis, and family history of HCC could be applied as an effective tool for risk prediction of HCC, which could discriminate at-risk individuals for precise prevention.
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Affiliation(s)
- Yuanlin Zou
- Department of Epidemiology and Statistics, College of Public HealthZhengzhou UniversityZhengzhouHenan ProvinceChina
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & TreatmentZhengzhou UniversityZhengzhouHenan ProvinceChina
| | - Jicun Zhu
- Department of PharmacyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina
| | - Caijuan Song
- The Institution for Chronic and Noncommunicable Disease Control and PreventionZhengzhou Center for Disease Control and PreventionZhengzhouHenan ProvinceChina
| | - Tiandong Li
- Department of Epidemiology and Statistics, College of Public HealthZhengzhou UniversityZhengzhouHenan ProvinceChina
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & TreatmentZhengzhou UniversityZhengzhouHenan ProvinceChina
| | - Keyan Wang
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & TreatmentZhengzhou UniversityZhengzhouHenan ProvinceChina
- Henan Institute of Medical and Pharmaceutical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina
| | - Jianxiang Shi
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & TreatmentZhengzhou UniversityZhengzhouHenan ProvinceChina
- Henan Institute of Medical and Pharmaceutical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina
| | - Hua Ye
- Department of Epidemiology and Statistics, College of Public HealthZhengzhou UniversityZhengzhouHenan ProvinceChina
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & TreatmentZhengzhou UniversityZhengzhouHenan ProvinceChina
| | - Peng Wang
- Department of Epidemiology and Statistics, College of Public HealthZhengzhou UniversityZhengzhouHenan ProvinceChina
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & TreatmentZhengzhou UniversityZhengzhouHenan ProvinceChina
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Floreani A, Gabbia D, De Martin S. Current Perspectives on the Molecular and Clinical Relationships between Primary Biliary Cholangitis and Hepatocellular Carcinoma. Int J Mol Sci 2024; 25:2194. [PMID: 38396870 PMCID: PMC10888596 DOI: 10.3390/ijms25042194] [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: 01/18/2024] [Revised: 02/07/2024] [Accepted: 02/09/2024] [Indexed: 02/25/2024] Open
Abstract
Primary biliary cholangitis (PBC) is an autoimmune liver disease characterised by the immune-mediated destruction of small and medium intrahepatic bile ducts, with variable outcomes and progression. This review summarises the state of the art regarding the risk of neoplastic progression in PBC patients, with a particular focus on the molecular alterations present in PBC and in hepatocellular carcinoma (HCC), which is the most frequent liver cancer in these patients. Major risk factors are male gender, viral infections, e.g., HBV and HCV, non-response to UDCA, and high alcohol intake, as well as some metabolic-associated factors. Overall, HCC development is significantly more frequent in patients with advanced histological stages, being related to liver cirrhosis. It seems to be of fundamental importance to unravel eventual dysfunctional molecular pathways in PBC patients that may be used as biomarkers for HCC development. In the near future, this will possibly take advantage of artificial intelligence-designed algorithms.
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Affiliation(s)
- Annarosa Floreani
- University of Padova, 35122 Padova, Italy;
- Scientific Consultant IRCCS Negrar, 37024 Verona, Italy
| | - Daniela Gabbia
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy;
| | - Sara De Martin
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy;
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Xu Z, Tang W, Xie Q, Cao X, Zhang M, Zhang X, Chai J. Dimethyl fumarate attenuates cholestatic liver injury by activating the NRF2 and FXR pathways and suppressing NLRP3/GSDMD signaling in mice. Exp Cell Res 2023; 432:113781. [PMID: 37722551 DOI: 10.1016/j.yexcr.2023.113781] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 08/27/2023] [Accepted: 09/12/2023] [Indexed: 09/20/2023]
Abstract
The progression of cholestasis is characterized by excessive accumulation of bile acids (BAs) in the liver, which leads to oxidative stress (OS), inflammation and liver injury. There are currently limited treatments for cholestasis. Therefore, appropriate drugs for cholestasis treatment need to be developed. Dimethyl fumarate (DMF) has been widely used in the treatment of various diseases and exerts antioxidant and anti-inflammatory effects, but its effect on cholestatic liver disease remains unclarified. We fed mice 3,5-diethoxycarbonyl-1,4-dihydrocollidine or cholic acid to induce cholestatic liver injury and treated these mice with DMF to evaluate its protective ability. Alanine aminotransferase, aspartate aminotransferase, and total liver BAs were assessed as indicators of liver function. The levels of OS, liver inflammation, transporters and metabolic enzymes were also measured. DMF markedly altered the relative ALT and AST levels and enhanced the liver antioxidant capacity. DMF regulated the MST/NRF2 signaling pathway to protect against OS and reduced liver inflammation through the NLRP3/GSDMD signaling pathway. DMF also regulated the levels of BA transporters by promoting FXR protein expression. These findings provide new strategies for the treatment of cholestatic liver disorders.
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Affiliation(s)
- Ziqian Xu
- School of Medicine, Chongqing University, Chongqing 400030, China; Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Center, and Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Wan Tang
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Center, and Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Qiaoling Xie
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Center, and Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Xinyu Cao
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Center, and Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Mengni Zhang
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Center, and Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Xiaoxun Zhang
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Center, and Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing 400038, China.
| | - Jin Chai
- School of Medicine, Chongqing University, Chongqing 400030, China; Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Center, and Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing 400038, China; The Second Affiliated Hospital, University of South China, Hengyang 421001, China.
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Braga MH, Cançado GGL, Bittencourt PL, Couto CA, Guedes LV, Lima AMC, Ferraz MLG, Villela-Nogueira CA, Nardelli MJ, Faria LC, Gomes NMDF, Oliveira EMG, Rotman V, Oliveira MB, da Cunha SMCF, Cunha-Silva M, Mendes LSC, Ivantes CAP, Codes L, de Almeida E Borges VF, Pace FHDL, Pessoa MG, Signorelli IV, Coral GP, Filho JG, Chagas AL, Terrabuio DRB, Cançado ELR. Risk factors for cancer in patients with primary biliary cholangitis and autoimmune hepatitis and primary biliary cholangitis overlap syndrome. Ann Hepatol 2023; 28:101105. [PMID: 37088418 DOI: 10.1016/j.aohep.2023.101105] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 03/01/2023] [Accepted: 03/16/2023] [Indexed: 04/25/2023]
Abstract
INTRODUCTION AND OBJECTIVES Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) and PBC overlap syndrome (AIH/PBC) have been associated with a higher risk of hepatocellular carcinoma (HCC) and extra-hepatic malignancy (EHM). This study aims to assess potential risk factors associated with cancer development in PBC and AIH/PBC. MATERIALS AND METHODS The Brazilian Cholestasis Study Group database was reviewed to compare clinical and laboratory features of PBC patients with HCC and EHM with those without cancer. RESULTS Among the 752 PBC patients enrolled, 64 of them with AIH/PBC, 87 cancers were identified in 72 patients, including 20 cases of HCC and 67 of EHM. Patients with HCC had a higher prevalence of cirrhosis (95% vs. 32.5% of those subjects without cancer, p≤0.001), smoking (55% vs. 12.3%, p≤0.001), CREST syndrome (30% vs 7.6%, p=0.003) and prior azathioprine (30% vs 8%, p= 0.005) and prednisone (35% vs 14%, p= 0.018) use, whereas patients with EHM had a higher prevalence of smoking (42.3% vs 12.4% of those subjects without cancer, p= <0.001), AMA positivity (96.6% vs 80.1%, p≤0.001), azathioprine therapy (21% vs 7.9%, p= 0.01) and concurrent other autoimmune diseases. In multivariate analysis, cirrhosis, obesity and prior azathioprine therapy were independent risk factors for HCC, while Sjogren syndrome and psoriasis were associated with EHM. Fibrates reduced EHM risk. CONCLUSIONS The prevalence of EHM is higher when compared to HCC in PBC patients. Cirrhosis, obesity, prior azathioprine use, and concurrent autoimmune diseases were significantly associated with cancer in PBC.
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Affiliation(s)
- Michelle Harriz Braga
- Departamento de Gastroenterologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil
| | - Guilherme Grossi Lopes Cançado
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Hospital da Polícia Militar de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
| | - Paulo Lisboa Bittencourt
- Escola Bahiana de Medicina e Saúde Pública, Salvador, Bahia, Brazil; Hospital Português, Salvador, Bahia, Brazil
| | - Cláudia Alves Couto
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Laura Vilar Guedes
- Departamento de Gastroenterologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil
| | - André Mourão Costa Lima
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Maria Lucia Gomes Ferraz
- Disciplina de Gastroenterologia, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil
| | - Cristiane Alves Villela-Nogueira
- Hospital Universitário Clementino Fraga Filho e Departamento de Clínica Médica da Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil
| | - Mateus Jorge Nardelli
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Luciana Costa Faria
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | | | | | - Vivian Rotman
- Hospital Universitário Clementino Fraga Filho e Departamento de Clínica Médica da Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil
| | - Maria Beatriz Oliveira
- Ambulatório Municipal de Hepatites Virais de São José dos Campos, São José dos Campos, São Paulo, Brazil
| | | | - Marlone Cunha-Silva
- Divisão de Gastroenterologia (Gastrocentro), Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil
| | | | | | | | - Valéria Ferreira de Almeida E Borges
- Instituto de Gastroenterologia, Endoscopia e Proctologia, Uberlândia, Minas Gerais, Brazil; Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil
| | - Fabio Heleno de Lima Pace
- Serviço de Gastroenterologia e Hepatologia, Universidade Federal de Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil
| | - Mario Guimarães Pessoa
- Departamento de Gastroenterologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil
| | - Izabelle Venturini Signorelli
- Hospital Universitário Cassiano Antônio Moraes, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil
| | - Gabriela Perdomo Coral
- Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
| | - João Galizzi Filho
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Aline Lopes Chagas
- Departamento de Gastroenterologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil
| | | | - Eduardo Luiz Rachid Cançado
- Departamento de Gastroenterologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil
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Xu H, Wu Z, Feng F, Li Y, Zhang S. Low vitamin D concentrations and BMI are causal factors for primary biliary cholangitis: A mendelian randomization study. Front Immunol 2022; 13:1055953. [PMID: 36605198 PMCID: PMC9807903 DOI: 10.3389/fimmu.2022.1055953] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 12/06/2022] [Indexed: 12/24/2022] Open
Abstract
Backgrounds Observational studies have identified associations between smoking, alcohol use, body mass index (BMI), and the levels of vitamin D with primary biliary cholangitis (PBC). However, there was a lack of randomization control studies to estimate the causal relationship. This study was to investigate the causal estimates for the effects of those risk factors on PBC. Methods The genetic instrument variants were extracted from genome-wide association studies in European ancestry. Two-sample mendelian randomization (MR) and multivariable mendelian randomization were used to determine genetically causal estimates. Primary analyses consisted of random-effects and fix-mode inverse-variance-weighted methods, followed by secondary sensitivity analyses to verify the results. Results Our study showed that BMI was a causal factor for PBC (OR 1.35; 95% CI=1.03-1.77; p=0.029). In addition, we found that serum vitamin D levels had a protective effect on PBC after adjusting for BMI (OR 0.51; 95% CI=0.32-0.84; p=0.007). However, we failed to identify evidence supporting that genetic causal effect of smoking and alcohol intake were associated with PBC in European countries. Conclusion Our results enriched findings from previous epidemiology studies and provided evidence from MR that serum vitamin D concentrations and BMI were independent causal factors for PBC, suggesting that ensuing vitamin D sufficiency and healthy lifestyles might be a cost-effective measure for early intervention for PBC.
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Affiliation(s)
- Honglin Xu
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science and Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Ziyan Wu
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Futai Feng
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science and Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Yongzhe Li
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,*Correspondence: Shulan Zhang, ; Yongzhe Li,
| | - Shulan Zhang
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science and Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China,*Correspondence: Shulan Zhang, ; Yongzhe Li,
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Abstract
Hepatocellular carcinoma (HCC) is potentially fatal complication affecting patients with primary biliary cholangitis (PBC). The incidence of HCC is 13 per 1000 person-years in patients with PBC cirrhosis, but much lower at 2.7 per 1000 person-years among patients with PBC without cirrhosis. Risk factors for the development of HCC in PBC include the presence of advanced fibrosis or cirrhosis and male sex, with some studies suggesting that treatment with ursodeoxycholic acid (UDCA) and UDCA response may reduce risk.
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Micali C, Russotto Y, Caci G, Ceccarelli M, Marino A, Celesia BM, Pellicanò GF, Nunnari G, Venanzi Rullo E. Loco-Regional Treatments for Hepatocellular Carcinoma in People Living with HIV. Infect Dis Rep 2022; 14:43-55. [PMID: 35076514 PMCID: PMC8788283 DOI: 10.3390/idr14010006] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 01/03/2022] [Accepted: 01/04/2022] [Indexed: 02/05/2023] Open
Abstract
Hepatocellular carcinoma (HCC) accounts for approximately 75-90% of primary liver cancers and is the sixth most common cancer and the third leading cause of cancer-related deaths worldwide. In the HIV-positive population, the risk of HCC is approximately four times higher than in the general population, with higher cancer-specific mortality than in HIV-negative patients. In most cases, HCC diagnosis is made in patients younger than the HIV-negative population and in the intermediate-advanced stage, thus limiting the therapeutic possibilities. Treatment choice in HIV-positive patients with HCC is subject to cancer staging, liver function and health status, as for HIV-negative and non-HIV-negative HCC patients. There are relatively few studies on the efficacy and safety in HIV-positive patients to date in loco-regional treatments for HCC. So far, literature shows that curative treatments such as radiofrequency ablation (RFA) have no significant differences in overall survival between HIV-positive and HIV-negative patients, as opposed to palliative treatments such as TACE, where there is a significant difference in overall survival. Although it can be assumed that the most recently discovered loco-regional therapies are applicable to HIV-positive patients with HCC in the same way as HIV-negative patients, further studies are needed to confirm this hypothesis. The purpose of our review is to evaluate these treatments, their efficacy, effectiveness, safety and their applicability to HIV-positive patients.
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Affiliation(s)
- Cristina Micali
- Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy; (Y.R.); (G.C.); (G.N.); (E.V.R.)
| | - Ylenia Russotto
- Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy; (Y.R.); (G.C.); (G.N.); (E.V.R.)
| | - Grazia Caci
- Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy; (Y.R.); (G.C.); (G.N.); (E.V.R.)
| | - Manuela Ceccarelli
- Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Catania, 95131 Catania, Italy; (M.C.); (A.M.); (B.M.C.)
- Unit of Infectious Diseases, Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, 98124 Messina, Italy
| | - Andrea Marino
- Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Catania, 95131 Catania, Italy; (M.C.); (A.M.); (B.M.C.)
| | - Benedetto Maurizio Celesia
- Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Catania, 95131 Catania, Italy; (M.C.); (A.M.); (B.M.C.)
| | - Giovanni Francesco Pellicanò
- Unit of Infectious Diseases, Department of Adult and Childhood Human Pathology “Gaetano Barresi”, University of Messina, 98124 Messina, Italy;
| | - Giuseppe Nunnari
- Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy; (Y.R.); (G.C.); (G.N.); (E.V.R.)
| | - Emmanuele Venanzi Rullo
- Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy; (Y.R.); (G.C.); (G.N.); (E.V.R.)
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Hepatocellular carcinoma in primary sclerosing cholangitis and primary biliary cholangitis: a clinical and pathological study in an uncommon but emerging setting. Virchows Arch 2021; 479:1131-1143. [PMID: 34414507 DOI: 10.1007/s00428-021-03183-6] [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: 04/18/2021] [Revised: 08/01/2021] [Accepted: 08/10/2021] [Indexed: 11/09/2022]
Abstract
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are biliary tract pathologies with increased risk of HCC, although HCC is more commonly associated with viral hepatitis and steatohepatitis. HCC risk stratification in PBC/PSC populations may help select patients for surveillance. We hypothesized that metabolic syndrome associated diagnoses and co-morbid nonalcoholic fatty liver disease (NAFLD) may be risk factors for HCC in patients with PBC and PSC. We undertook a multi-institutional case control study of PSC (19 cases, 38 controls) and PBC (39 cases and controls) patients with advanced fibrosis, matched for known HCC risk factors of age and sex, who had native liver explant or resection specimens. In the PSC population, HCC risk was significantly associated with multiple metabolic syndrome associated diagnoses (OR 13, p = 0.02), hyperlipidemia (OR 29, p = 0.03), and obesity (OR 6.8, p = 0.01). In the PBC cohort, only type 2 diabetes was a risk factor for HCC (OR 4.7, p = 0.03). In the PSC cohort, thick fibrous septae were associated with HCC risk (OR 3.4, p = 0.04). No other pathologic features of the nonneoplastic liver were significantly associated with HCC, including features of NAFLD such as macrovesicular steatosis, pericellular fibrosis, and steatohepatitis. Metabolic syndrome associated diagnoses, specifically type 2 diabetes among PBC patients, is associated with HCC risk in patients with biliary type cirrhosis. However, we found no evidence that HCC risk is related to co-morbid NAFLD, indicating a likely distinct mechanism of metabolic syndrome-associated carcinogenesis in these populations.
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Natarajan Y, Tansel A, Patel P, Emologu K, Shukla R, Qureshi Z, El-Serag HB, Thrift AP, Kanwal F. Incidence of Hepatocellular Carcinoma in Primary Biliary Cholangitis: A Systematic Review and Meta-Analysis. Dig Dis Sci 2021; 66:2439-2451. [PMID: 32743773 DOI: 10.1007/s10620-020-06498-7] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Accepted: 07/18/2020] [Indexed: 01/17/2023]
Abstract
BACKGROUND The risk and determinants of HCC in patients with primary biliary cholangitis (PBC) are unclear. We conducted a systematic review and meta-analysis of the incidence of HCC and risk factors associated with HCC risk among patients with PBC. METHODS We searched PubMed, EMBASE, MEDLINE, Cochrane databases and reference lists from relevant articles to identify cohort studies that examined incidence of HCC in patients with PBC from inception through November 2019. RESULTS A total of 29 studies including 22,615 patients met the eligibility criteria. The median cohort size was 292 patients followed for an average of 76 months. The pooled incidence rate for patients with PBC was 4.17 per 1000 patient-years (95% CI 3.17-5.47). On subgroup analysis, the incidence of HCC in patients with PBC cirrhosis was 15.7 per 1000 patient-years (95% CI 8.73-28.24). The HCC incidence rate was 9.82 per 1000 person-years (95% CI 5.92-16.28) in men and 3.82 per 1000 person-years (95% CI 2.85-5.11) in women. CONCLUSIONS Cirrhosis is the strongest risk factor for HCC in patients with PBC. Male gender was also a risk factor. Our meta-analysis supports current recommendations of HCC surveillance in patients with PBC cirrhosis. Further studies are needed to evaluate risk factors in this population.
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Affiliation(s)
- Yamini Natarajan
- Section of Gastroenterology and Hepatology and Clinical Epidemiology and Comparative Effectiveness Program in the Health Services Research, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd (MS152), Houston, TX, 77030, USA.
| | - Aylin Tansel
- Section of Gastroenterology and Hepatology and Clinical Epidemiology and Comparative Effectiveness Program in the Health Services Research, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd (MS152), Houston, TX, 77030, USA
| | - Parth Patel
- Section of Gastroenterology and Hepatology and Clinical Epidemiology and Comparative Effectiveness Program in the Health Services Research, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd (MS152), Houston, TX, 77030, USA
| | - Kingsley Emologu
- Section of Gastroenterology and Hepatology and Clinical Epidemiology and Comparative Effectiveness Program in the Health Services Research, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd (MS152), Houston, TX, 77030, USA
| | - Richa Shukla
- Section of Gastroenterology and Hepatology and Clinical Epidemiology and Comparative Effectiveness Program in the Health Services Research, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd (MS152), Houston, TX, 77030, USA
| | - Zeeshan Qureshi
- Section of Gastroenterology and Hepatology and Clinical Epidemiology and Comparative Effectiveness Program in the Health Services Research, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd (MS152), Houston, TX, 77030, USA
| | - Hashem B El-Serag
- Section of Gastroenterology and Hepatology and Clinical Epidemiology and Comparative Effectiveness Program in the Health Services Research, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd (MS152), Houston, TX, 77030, USA.,Clinical Epidemiology and Comparative Effectiveness Program, Section of Health Services Research (IQuESt), Michael E. DeBakey VA Medical Center, Baylor College of Medicine, Houston, TX, USA.,Texas Medical Center Digestive Disease Center, Houston, TX, USA.,Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine, Houston, TX, USA
| | - Aaron P Thrift
- Section of Gastroenterology and Hepatology and Clinical Epidemiology and Comparative Effectiveness Program in the Health Services Research, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd (MS152), Houston, TX, 77030, USA.,Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine, Houston, TX, USA
| | - Fasiha Kanwal
- Section of Gastroenterology and Hepatology and Clinical Epidemiology and Comparative Effectiveness Program in the Health Services Research, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd (MS152), Houston, TX, 77030, USA.,Clinical Epidemiology and Comparative Effectiveness Program, Section of Health Services Research (IQuESt), Michael E. DeBakey VA Medical Center, Baylor College of Medicine, Houston, TX, USA.,Texas Medical Center Digestive Disease Center, Houston, TX, USA.,Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine, Houston, TX, USA
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Clinical application of thioredoxin reductase as a novel biomarker in liver cancer. Sci Rep 2021; 11:6069. [PMID: 33727662 PMCID: PMC7966739 DOI: 10.1038/s41598-021-85688-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 02/26/2021] [Indexed: 12/24/2022] Open
Abstract
Hepatic cancer is often amenable to surgery, including percutaneous ablation, trans-arterial chemoembolization. However, in metastatic cases, surgery is often not an effective option. Chemotherapy as a conventional clinical method for treatment of malignant diseases may be useful in such cases, but it is likewise not always able to slow or halt progression, therefore novel approaches for treatment of hepatic cancer are needed. Current research suggests that molecular tumor markers (TM) can play a crucial role for diagnosis and prognostic evaluation of malignancies, and TM such as AFP, CEA, CA19-9 have been reported in many malignant diseases. Thioredoxin reductase (TrxR), a type of anti-oxidant biomarker, has become a TM of significant interest. However, little is known about the above TM and TrxR activity in liver cancer. Therefore, this paper aimed to assess these TM with regards to diagnosis and and monitoring treatment efficacy in both primary and metastatic liver cancer. Our results showed TrxR had superior performance for discriminating between liver cancer patients and healthy controls than AFP, CEA, and CA19-9. TrxR also exhibited superior performance for assessing benefits of chemotherapy regardless if patients had PLC or MLC. Meanwhile, due to diagnostic efficiency of unresponsive chemotherapy patients, TrxR also showed a higher activity levels than other general markers in liver metastasis patients. Our results suggest that application of TrxR in combination with other tumor markers may maximize the efficiency of diagnosis and assessment of therapeutic efficiency, and provide new insights for the clinical application of TrxR as a candidate biomarker for liver cancer.
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Rigopoulou EI, Dalekos GN. Current Trends and Characteristics of Hepatocellular Carcinoma in Patients with Autoimmune Liver Diseases. Cancers (Basel) 2021; 13:1023. [PMID: 33804480 PMCID: PMC7957658 DOI: 10.3390/cancers13051023] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 02/17/2021] [Accepted: 02/24/2021] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC), the commonest among liver cancers, is one of the leading causes of mortality among malignancies worldwide. Several reports demonstrate autoimmune liver diseases (AILDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) to confer increased risk of hepatobiliary malignancies, albeit at lower frequencies compared to other liver diseases. Several parameters have been recognized as risk factors for HCC development in AIH and PBC, including demographics such as older age and male sex, clinical features, the most decisive being cirrhosis and other co-existing factors, such as alcohol consumption. Moreover, biochemical activity and treatment response have been increasingly recognized as prognostic factors for HCC development in AIH and PBC. As available treatment modalities are effective only when HCC diagnosis is established early, surveillance has been proven essential for HCC prognosis. Considering that the risk for HCC is not uniform between and within disease groups, refinement of screening strategies according to prevailing demographic, clinical, and molecular risk factors is mandated in AILDs patients, as personalized HCC risk prediction will offer significant advantage in patients at high and/or medium risk. Furthermore, future investigations should draw attention to whether modification of immunosuppression could benefit AIH patients after HCC diagnosis.
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Affiliation(s)
| | - George N. Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, 41110 Larissa, Greece;
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The clinical and laboratory features associated with cancer in patients with primary biliary cholangitis: a longitudinal survey-based study. Clin Rheumatol 2021; 40:3311-3317. [PMID: 33611649 DOI: 10.1007/s10067-021-05657-z] [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: 10/26/2020] [Revised: 02/02/2021] [Accepted: 02/16/2021] [Indexed: 10/22/2022]
Abstract
OBJECTIVES To analyze the clinical and laboratory features of primary biliary cholangitis (PBC) patients complicated with cancer, and explore the potential factors associated with cancer. METHODS We consecutively enrolled PBC patients from January 2002 to February 2016 in Peking Union Medical College Hospital and performed a structured interview, systemic rheumatologic evaluation, and laboratory tests. The risk factors associated with cancer were analyzed with univariate and multivariable logistic regression and proportional hazard model. RESULTS Among the 580 PBC patients enrolled, 51 cancers were identified in 51 patients (8.8%), including 45 (88.2%) solid tumors and 6 (11.8%) hematologic malignancies. Patients with cancer were older (62.1 ± 9.6 vs. 55.4 ± 11.6 years, p < 0.01) than patients without cancer. Additionally, positive anti-centromere antibody (ACA) was more frequently observed in patients without cancer (25.9% vs 4.3%, p = 0.019) compared with patients with cancer diagnosed after establishing PBC. The median follow-up after the diagnosis of PBC was 4 years (IQR 2.0-6.6). Furthermore, multivariable logistic regression confirmed that older age was associated with cancer in PBC patients (odds ratio (OR) = 1.045, 95% confidence interval (CI): 1.006-1.085), and positive ACA was a protective factor (OR = 0.116, 95% CI: 0.015-0.876). Additionally, proportional hazard model analysis revealed that age was a risk factor (hazard ratio = 1.045, 95% CI: 1.012-1.080), and positive ACA was a protective factor (hazard ratio = 0.232, 95% CI: 0.055-0.977) for cancer. CONCLUSIONS Both solid tumor and hematologic malignancy were prevalent in PBC patients. Older age was associated with cancer, and positive ACA was a protective factor of cancer in PBC patients. Key Points • Patients with PBC could present with both solid tumors and hematologic malignancies. • Multivariable logistic regression and proportional hazard model analysis revealed that age was a risk factor as we know, and positive ACA was a protective factor.
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Lleo A, Wang GQ, Gershwin ME, Hirschfield GM. Primary biliary cholangitis. Lancet 2020; 396:1915-1926. [PMID: 33308474 DOI: 10.1016/s0140-6736(20)31607-x] [Citation(s) in RCA: 147] [Impact Index Per Article: 29.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 06/27/2020] [Accepted: 07/10/2020] [Indexed: 12/14/2022]
Abstract
Primary biliary cholangitis is an autoimmune liver disease that predominantly affects women. It is characterised by a chronic and destructive, small bile duct, granulomatous lymphocytic cholangitis, with typical seroreactivity for antimitochondrial antibodies. Patients have variable risks of progressive ductopenia, cholestasis, and biliary fibrosis. Considerations for the cause of this disease emphasise an interaction of chronic immune damage with biliary epithelial cell responses and encompass complex, poorly understood genetic risks and environmental triggers. Licensed disease-modifying treatment focuses on amelioration of cholestasis, with weight-dosed oral ursodeoxycholic acid. For patients who do not respond sufficiently, or patients with ursodeoxycholic acid intolerance, conditionally licensed add-on therapy is with the FXR (NR1H4) agonist, obeticholic acid. Off-label therapy is recognised as an alternative, notably with the pan-PPAR agonist bezafibrate; clinical trial agents are also under development. Baseline characteristics, such as young age, male sex, and advanced disease, and serum markers of liver injury, particularly bilirubin and ALP, are used to stratify risk and assess treatment responsiveness. Parallel attention to the burden of patient symptoms is paramount, including pruritus and fatigue.
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Affiliation(s)
- Ana Lleo
- Department of Biomedical Sciences, Humanitas University, Milan, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Clinical and Research Center IRCCS, Rozzano, Italy
| | - Giu-Qiang Wang
- Department of Infectious Diseases and Center for Liver Diseases, Peking University First Hospital, Beijing, China; Department of Infectious Diseases and Liver Diseases, Peking University International Hospital, Beijing, China
| | - Merrill Eric Gershwin
- Division of Rheumatology, Allergy and Clinical Immunology, The University of California, Davis, CA, USA
| | - Gideon M Hirschfield
- Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University of Toronto, Toronto, ON, Canada.
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Gender Matters: Characteristics of Hepatocellular Carcinoma in Women From a Large, Multicenter Study in the United States. Am J Gastroenterol 2020; 115:1486-1495. [PMID: 32453046 DOI: 10.14309/ajg.0000000000000643] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide, affecting men to women at a ratio of about 4:1. Risk factors, characteristics, and outcomes for HCC in women in the United States remain poorly understood; therefore, we aim to explore gender differences further. METHODS Patients diagnosed with HCC between January 2000 and June 2014 at 5 large centers were identified. Clinical information, tumor characteristics, and survival data were extracted manually. The presence of underlying cirrhosis was assessed based on published criteria. RESULTS Of 5,327 patients with HCC in our cohort, 1,203 (22.6%) were women. There were important differences in the underlying etiology of liver disease between the 2 genders (P < 0.0001): women had a significantly higher frequency of nonalcoholic fatty liver disease (23% vs 12%) and lower frequency of alcoholic liver disease (5% vs 15%). The proportion of noncirrhotic HCC was significantly higher among women (17% vs 10%, P < 0.0001). Women had less-advanced HCC at presentation by tumor, node, metastasis staging (P < 0.0001) and a higher proportion within Milan criteria (39% vs 35%, P = 0.002). Women had a greater overall survival (2.5 ± 2.9 years vs 2.2 ± 2.7 years, P = 0.0031). DISCUSSION The frequency of underlying nonalcoholic fatty liver disease and noncirrhotic HCC were significantly higher in women than men in this large cohort. Women presented with less-advanced HCC and had a greater overall survival. Further investigation is warranted to explore potential mechanisms and implications for these gender differences, especially with noncirrhotic HCC (see Visual Abstract, Supplementary Digital Content 1, http://links.lww.com/AJG/B535).
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Drazilova S, Babinska I, Gazda J, Halanova M, Janicko M, Kucinsky B, Safcak D, Martinkova D, Tarbajova L, Cekanova A, Jarcuska P. Epidemiology and clinical course of primary biliary cholangitis in Eastern Slovakia. Int J Public Health 2020; 65:683-691. [PMID: 32500239 DOI: 10.1007/s00038-020-01391-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Revised: 05/13/2020] [Accepted: 05/13/2020] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVE To determine both the incidence and the prevalence of primary biliary cholangitis (PBC) in Eastern Slovakia and to describe its clinical course and the response to ursodeoxycholic acid (UDCA). METHODS We recorded data of patients with PBC, who were followed up in gastroenterology and hepatology centers in Eastern Slovakia during the period from June 30, 1999, through June 30, 2019. RESULTS The annual incidence of PBC varied from 0.7 to 1.5 cases per 100,000 inhabitants between 2014 and 2018. PBC prevalence steadily increased from initial 10.2 cases per 100,000 inhabitants in 2014 to 14.9 cases per 100,000 inhabitants in June 2019. The mean age at the time of diagnosis was 56.3 ± 10.9 years. 95.7% of patients were females, and female/male gender ratio was 22.3:1. In June 2019, prevalence in the female population was 28 cases per 100,000 women. At the time of diagnosis, three-quarters of patients were symptomatic and 10% of patients had liver cirrhosis. The mean follow-up was 7.3 ± 5.2 years. Response to UDCA was observed in 72.1% of patients. Patients with higher baseline alkaline phosphatase (ALP) levels, liver cirrhosis at entry or at the end of follow-up and women younger than 45 years responded worse to UDCA. One-quarter of patients had liver cirrhosis at the end of follow-up. During follow-up, 1.6% of patients underwent liver transplantation and 5.5% of patients died. Five-year and 10-year liver-related mortalities were 2.7% and 4.3%, respectively. CONCLUSION PBC prevalence in Eastern Slovakia is increasing, and most of the patients respond to therapy with UDCA.
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Affiliation(s)
- Sylvia Drazilova
- Department of Internal Medicine, Hospital Poprad, Poprad, Slovakia
| | - Ingrid Babinska
- Department of Epidemiology, PJ Safarik University, Faculty of Medicine, Kosice, Slovakia.
| | - Jakub Gazda
- 2nd Department of Internal Medicine, Faculty of Medicine and L Pasteur University Hospital, PJ Safarik University, Kosice, Slovakia
| | - Monika Halanova
- Department of Epidemiology, PJ Safarik University, Faculty of Medicine, Kosice, Slovakia
| | - Martin Janicko
- 2nd Department of Internal Medicine, Faculty of Medicine and L Pasteur University Hospital, PJ Safarik University, Kosice, Slovakia
| | - Branislav Kucinsky
- 2nd Department of Internal Medicine, Faculty of Medicine and L Pasteur University Hospital, PJ Safarik University, Kosice, Slovakia
| | - Dominik Safcak
- 2nd Department of Internal Medicine, Faculty of Medicine and L Pasteur University Hospital, PJ Safarik University, Kosice, Slovakia
- Department of Radiotherapy and Oncology, Faculty of Medicine and Eastern Slovakia Institute of Oncology Kosice, PJ Safarik University, Kosice, Slovakia
| | | | - Lucia Tarbajova
- Department of Internal Medicine, Hospital Poprad, Poprad, Slovakia
| | - Anna Cekanova
- 2nd Department of Internal Medicine, Faculty of Medicine and L Pasteur University Hospital, PJ Safarik University, Kosice, Slovakia
| | - Peter Jarcuska
- 2nd Department of Internal Medicine, Faculty of Medicine and L Pasteur University Hospital, PJ Safarik University, Kosice, Slovakia
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Epidemiology and clinical course of primary biliary cholangitis in the Asia-Pacific region: a systematic review and meta-analysis. Hepatol Int 2019; 13:788-799. [PMID: 31552558 DOI: 10.1007/s12072-019-09984-x] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Accepted: 08/22/2019] [Indexed: 12/12/2022]
Abstract
AIMS Epidemiological studies on primary biliary cholangitis (PBC) show heterogeneity. The aim of the present study was to synthesize the prevalence, incidence and clinical course of PBC in the Asia-Pacific region. METHODS PubMed, Medline, Cochrane library and EMBASE were searched for epidemiology and clinical course of PBC published up to July, 2019. Meta-analysis was conducted on the epidemiology and clinical course (decompensation, hepatocellular carcinoma and death/liver transplantation) of PBC patients. Random-effect model and fixed-effect model were used to evaluate the pooled prevalence, incidence, mortality/liver transplantation and their 95% confidence intervals as appropriate. Subgroup analysis was performed by stratification with gender, pre- and post-UDCA era, sub-region and publication year. Meta-regression was used to examine the heterogeneity. RESULTS Out of 3460 studies, 18 studies from 7 countries/regions were finally included. The overall prevalence of PBC was 118.75 cases per million (95% CI 49.96-187.55) in the Asia-Pacific region, with the high, medium and low prevalence being in Japan and China (191.18 cases per million), New Zealand (99.16 cases per million) and South Korea and Australia (39.09 cases per million), respectively. The incidence of PBC was 8.55 cases per million per year (95% CI 8.05-9.06). The 5-year accumulative incidence of decompensation, HCC and death/liver transplantation in PBC patients was 6.95% (95% CI 2.07-11.83%), 1.54% (95% CI 0.9-2.19%) and 4.02% (95% CI 2.49-5.54%), respectively. CONCLUSION In the Asia-Pacific region, the prevalence and incidence of PBC are higher than once expected. PBC tends to be diagnosed at older age and has a relatively low incidence of HCC in this region.
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Sun Q, Wang Q, Feng N, Meng Y, Li B, Luo D, Shang X, Lv J, Monsaf AM, Wang C, Ma X. The expression and clinical significance of serum IL-17 in patients with primary biliary cirrhosis. ANNALS OF TRANSLATIONAL MEDICINE 2019; 7:389. [PMID: 31555703 DOI: 10.21037/atm.2019.07.100] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Background We aimed to investigate the expression and clinical significance of interleukin 17 (IL-17) in patients with primary biliary cirrhosis (PBC). Methods PBC patients (n=127), patients without PBC (n=100) were selected from January 2015 to December 2015.The measure of IL-17 level was performed by cytometric beads array (CBA), immunohistochemistry and real-time PCR (QRT-PCR). Results The expression levels of serum IL-17, IL-6, IFN-γ, TNF-α and IL-10 in PBC groups were significantly higher than control group, a positively correlation between IL-17 and ALT, ALP, GGT, CIV was observed in PBC patients (r=0.350, P=0.013; r=0.373, P=0.008; r=0.337, P=0.017; r=0.349, P=0.021). In addition, IL-17 mRNA expression level in PBC group was higher than control group. Immunohistochemical results suggest that positive cells did not appear in normal tissues, while they appeared in the PBC liver tissue, mainly in the bile duct. Conclusions This study shows that IL-17 over expressed in PBC patients, it played a pro-inflammatory effect in the pathogenesis of PBC, most probably as a targeting drug research.
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Affiliation(s)
- Qiannan Sun
- Clinical Medical Research Institute, State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China.,College of Basic Medicine of Xinjiang Medical University, Urumqi 830011, China
| | - Qian Wang
- Clinical Medical Research Institute, State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China.,Department of Clinical Laboratory Center, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, China
| | - Ning Feng
- Clinical Medical Research Institute, State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China
| | - Yan Meng
- Clinical Medical Research Institute, State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China
| | - Bin Li
- College of Basic Medicine of Xinjiang Medical University, Urumqi 830011, China
| | - Demei Luo
- Clinical Medical Research Institute, State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China
| | - Xiaoqian Shang
- Clinical Medical Research Institute, State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China
| | - Jie Lv
- Clinical Medical Research Institute, State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China
| | - Ahmad Maqsuod Monsaf
- Clinical Medical Research Institute, State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China
| | - Changmin Wang
- Department of Clinical Laboratory Center, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, China
| | - Xiumin Ma
- Clinical Medical Research Institute, State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China.,College of Basic Medicine of Xinjiang Medical University, Urumqi 830011, China
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Abstract
PURPOSE OF REVIEW To discuss current knowledge and recent findings regarding the epidemiology of hepatocellular carcinoma (HCC) in the USA. RECENT FINDING The US incidence rate of HCC is increasing, although the pace may have somewhat slowed since 2010. In 2012, incidence rates of HCC in Hispanics surpassed those of Asians. The recent epidemiological changes in major risk factors for HCC include increasing hepatitis C virus post-sustained virologic response, suppressed hepatitis B virus on nucleoside analogues, and alcoholic and non-alcoholic fatty liver disease. Non-alcoholic fatty liver disease has the greatest proportion of the burden of the main risk factors for HCC in the USA, followed by alcoholic liver disease, and hepatitis C virus and hepatitis B virus infections. This review focuses on current knowledge regarding the recent epidemiological trends in HCC, with an emphasis on future directions.
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Tarao K, Nozaki A, Ikeda T, Sato A, Komatsu H, Komatsu T, Taguri M, Tanaka K. Real impact of liver cirrhosis on the development of hepatocellular carcinoma in various liver diseases-meta-analytic assessment. Cancer Med 2019; 8:1054-1065. [PMID: 30791221 PMCID: PMC6434205 DOI: 10.1002/cam4.1998] [Citation(s) in RCA: 109] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Revised: 12/27/2018] [Accepted: 01/06/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND It is well known that the incidence of developing hepatocelluler carcinoma (HCC) is increased in liver cirrhosis of different etiologies. However, comparison of HCC incidence in various liver diseases has not yet been estimated. We surveyed this comparison. METHODS The PubMed database was examined (1989-2017) for studies published in English language regarding the prospective follow-up results for the development of HCC in various liver diseases. A meta-analysis was performed for each liver disease. RESULTS The annual incidence (%) of HCC in the non-cirrhotic stage and cirrhotic stage, and the ratio of HCC incidence in the cirrhotic stage/non-cirrhotic stage were as follows. (a) hepatitis B virus liver disease: 0.37%→3.23% (8.73-fold), (b) hepatitis C virus liver diseases: 0.68%→4.81% (7.07-fold), (c) primary biliary cholangitis (0.26%→1.79%, 6.88-fold), (d) autoimmune hepatitis (0.19%→0.53%, 2.79-fold), and (e) NASH (0.03%→1.35%, 45.00-fold). Regarding primary hemochromatosis and alcoholic liver diseases, only follow-up studies in the cirrhotic stage were presented, 1.20% and 2.06%, respectively. CONCLUSIONS When the liver diseases advance to cirrhosis, the incidence of HCC is markedly increased. The development of HCC must be closely monitored by ultrasonography, magnetic resonance imaging, and computed tomography, irrespective of the different kinds of liver diseases.
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Affiliation(s)
- Kazuo Tarao
- Tarao’s Gastroenterological ClinicYokohamaJapan
| | - Akito Nozaki
- Gastroenterological Center, Medical CenterYokohama City UniversityYokohamaJapan
| | - Takaaki Ikeda
- Gastroenterology DepartmentYokosuka General Hospital UwamachiYokosukaJapan
| | - Akira Sato
- Division of Gastroenterology, Department of Internal MedicineSt. Marianna University, Yokohama City Seibu HospitalYokohamaJapan
| | - Hirokazu Komatsu
- Department of GastroenterologyYokohama Municipal Citizen’s HospitalYokohamaJapan
| | - Tatsuji Komatsu
- Department Clinical ResearchNational Hospital Organization, Yokohama Medical CenterYokohamaJapan
| | - Masataka Taguri
- Department of Data ScienceYokohama City UniversityYokohamaJapan
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Xu C, Luo L, Yu Y, Zhang Z, Zhang Y, Li H, Cheng Y, Qin H, Zhang X, Ma H, Li Y. Screening therapeutic targets of ribavirin in hepatocellular carcinoma. Oncol Lett 2018; 15:9625-9632. [PMID: 29805683 PMCID: PMC5958667 DOI: 10.3892/ol.2018.8552] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2016] [Accepted: 10/13/2017] [Indexed: 12/16/2022] Open
Abstract
The objective of the present study was to screen the key genes of ribavirin in hepatocellular carcinoma (HCC) and provide novel therapeutic targets for HCC treatment. The mRNA expression datasets of GSE23031 and GSE74656, as well as the microRNA (miRNA) expression dataset of GSE22058 were downloaded from the Gene Expressed Omnibus database. In the GSE23031 dataset, there were three HCC cell lines treated with PBS and three HCC cell lines treated with ribavirin. In the GSE74656 dataset, five HCC tissues and five carcinoma adjacent tissues were selected. In the GSE22058 dataset, 96 HCC tissues and 96 carcinoma adjacent tissues were selected. The differentially expressed genes (DEGs) and differentially expressed miRNAs were identified via the limma package of R. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed with the Database for Annotation, Visualization and Integrated Discovery. The target mRNAs of DEMs were obtained with TargetScan. A total of 559 DEGs (designated DEG-Ribavirin) were identified in HCC cells treated with ribavirin compared with PBS and 632 DEGs (designated DEG-Tumor) were identified in HCC tissues compared with carcinoma adjacent tissues. A total of 220 differentially expressed miRNAs were identified in HCC tissues compared with carcinoma adjacent tissues. In addition, 121 GO terms and three KEGG pathways of DEG-Ribavirin were obtained, and 383 GO terms and 25 KEGG pathways of DEG-Tumor were obtained. A total of five key miRNA-mRNA regulated pairs were identified, namely miR-183→CCNB1, miR-96→DEPDC1, miR-96→NTN4, miR-183→NTN4 and miR-145→NTN4. The present study indicated that certain miRNAs (including miR-96, miR-145 and miR-183) and mRNAs (including NAT2, FBXO5, CCNB1, DEPDC1 and NTN4) may be associated with the effects of ribavirin on HCC. Furthermore, they may provide novel therapeutic targets for HCC treatment.
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Affiliation(s)
- Chen Xu
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, P.R. China
| | - Liyun Luo
- Department of Cardiology, The Fifth Affiliated Hospital of Sun Yan-Sen University, Zhuhai, Guangdong 519000, P.R. China
| | - Yongjun Yu
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, P.R. China
| | - Zhao Zhang
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, P.R. China
| | - Yi Zhang
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, P.R. China
| | - Haimei Li
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, P.R. China
| | - Yue Cheng
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, P.R. China
| | - Hai Qin
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, P.R. China
| | - Xipeng Zhang
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, P.R. China
| | - Hongmei Ma
- Department of Nursing, Tianjin Union Medical Center, Tianjin 300121, P.R. China
| | - Yuwei Li
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, P.R. China
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Burman BE, Jhaveri MA, Kowdley KV. An Update on the Treatment and Follow-up of Patients with Primary Biliary Cholangitis. Clin Liver Dis 2017; 21:709-723. [PMID: 28987258 DOI: 10.1016/j.cld.2017.06.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by chronic granulomatous lymphocytic cholangitis of the small bile ducts. PBC was a leading indication for liver transplant in the United States; with early diagnosis and treatment, the majority of patients with PBC have a normal life expectancy. Pathogenesis involves inflammatory damage of bile duct epithelium secondary to innate and adaptive immune responses, and toxicity from accumulated bile acids. Cholestasis and disease progression can lead to cirrhosis. Extrahepatic complications include dyslipidemia, metabolic bone disease, and fat-soluble vitamin deficiency. Ursodeoxycholic acid is a well-established therapy. Novel targeted therapeutics are being developed.
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Affiliation(s)
- Blaire E Burman
- Division of Gastroenterology and Hepatology, Virginia Mason Medical Center, 1100 Ninth Avenue, Seattle, WA 98101, USA
| | - Manan A Jhaveri
- Department of Organ Transplant & Liver Center, Liver Care Network and Organ Care Research, Swedish Medical Center, Seattle, 1124 Columbia Street, WA 98101, USA
| | - Kris V Kowdley
- Department of Organ Transplant & Liver Center, Liver Care Network and Organ Care Research, Swedish Medical Center, Seattle, 1124 Columbia Street, WA 98101, USA.
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25
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Alcohol, smoking and the liver disease patient. Best Pract Res Clin Gastroenterol 2017; 31:537-543. [PMID: 29195673 DOI: 10.1016/j.bpg.2017.09.003] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Revised: 08/31/2017] [Accepted: 09/03/2017] [Indexed: 02/06/2023]
Abstract
Alcohol is an established risk factor for cirrhosis. Current recommendations for a "safe" limit for alcohol consumption are usually set to around 30 g of alcohol per day for men and 20 g per day for women, but evidence is mounting that these cut-offs might be set too high. Also, inter-individual differences in the hepatic sensitivity for alcohol likely play into the risk of development of cirrhosis. In patients with concomitant liver diseases, a synergistic effect on fibrosis progression and high consumption of alcohol is evident. The role of low to moderate consumption is less clear. Alcohol can also lead to a specific inflammatory state in the liver, alcoholic hepatitis (AH). Treatment of severe AH consists of corticosteroids, which are at best moderately effective, and new treatments are needed. Liver transplantation is an option in severe alcoholic liver disease, although selection of patients that are at a very low risk of post-transplantation alcohol consumption is paramount. There is some evidence to suggest an increased risk for fibrosis progression and development of hepatocellular carcinoma specifically for smoking.
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Tansel A, Katz LH, El-Serag HB, Thrift AP, Parepally M, Shakhatreh MH, Kanwal F. Incidence and Determinants of Hepatocellular Carcinoma in Autoimmune Hepatitis: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2017; 15:1207-1217.e4. [PMID: 28215616 PMCID: PMC5522646 DOI: 10.1016/j.cgh.2017.02.006] [Citation(s) in RCA: 68] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2016] [Revised: 01/31/2017] [Accepted: 02/06/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The risk of hepatocellular carcinoma (HCC) in patients with autoimmune hepatitis (AIH) is unclear. We conducted a systematic review and meta-analysis of the incidence of HCC and associated risk factors among patients with AIH. METHODS We searched PubMed, Embase, and reference lists from relevant articles through June 2016 to identify cohort studies that examined the incidence of HCC in patients with AIH. We used random effects models to estimate pooled incidence rates overall and in subgroup of patients with cirrhosis. The between-study heterogeneity was assessed using I2 statistic. RESULTS A total of 25 studies (20 papers and 5 abstracts), including 6528 patients, met the eligibility criteria. The median cohort size was 170 patients with AIH (range, 25-1721 patients), followed for a median of 8.0 years (range, 3.3-16.0 years). The pooled incidence rate for HCC in patients with AIH was 3.06 per 1000 patient-years (95% confidence interval, 2.22-4.23; I2 = 51.5%; P = .002). The pooled incidence of HCC in patients with cirrhosis at AIH diagnosis was 10.07 per 1000 patient-years (95% confidence interval, 6.89-14.70; I2 = 48.8%; P = .015). In addition, 92 of 93 patients who had HCC had evidence of cirrhosis before or at the time of their HCC diagnosis. The risk of HCC seems to be lower in patients with AIH and cirrhosis than that reported for patients with cirrhosis from hepatitis B, hepatitis C, or primary biliary cholangitis. CONCLUSIONS Based on the increased risked of HCC shown in this meta-analysis, there may be a role for HCC surveillance in patients with AIH and cirrhosis.
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Affiliation(s)
- Aylin Tansel
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas.
| | - Lior H Katz
- The Department of Gastroenterology, Sheba Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Hashomer, Israel
| | - Hashem B El-Serag
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas; Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Section of Gastroenterology and Hepatology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Aaron P Thrift
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas
| | - Mayur Parepally
- Division of Gastroenterology and Nutrition, Department of Medicine, Loyola University Medical Center, Chicago, Illinois
| | - Mohammad H Shakhatreh
- Section of Gastroenterology and Hepatology, Virginia Tech Carilion School of Medicine and Research Institute, Roanoke, Virginia
| | - Fasiha Kanwal
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas; Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Section of Gastroenterology and Hepatology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
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Abstract
Purpose of Review High consumption of alcohol can lead to cirrhosis. The risk of a low to moderate consumption of alcohol in the setting of a concurrent liver disease is less clear. The aim of this review is to sum the evidence on the risk of adverse outcomes in patients with liver diseases other than alcoholic liver disease who consume alcohol. Recent Findings High alcohol consumption is strongly associated with adverse outcomes in most liver diseases. For hepatitis C, some evidence points to an increased risk for fibrosis progression also with low amounts. For non-alcoholic fatty liver disease, most studies indicate an inverse association between fibrosis and alcohol consumption, but methodological limitations reduce inference. Summary High alcohol consumption is associated with an increased risk of fibrosis progression and other adverse outcomes, while less is clear regarding low to moderate consumption. Obtaining high-level evidence on this topic ought to be the objective of future studies. Currently, an individual risk profile should be obtained in patients with liver disease who consume alcohol.
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28
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Huang YQ. Recent advances in the diagnosis and treatment of primary biliary cholangitis. World J Hepatol 2016; 8:1419-1441. [PMID: 27957241 PMCID: PMC5124714 DOI: 10.4254/wjh.v8.i33.1419] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2016] [Revised: 07/26/2016] [Accepted: 08/29/2016] [Indexed: 02/06/2023] Open
Abstract
Primary biliary cholangitis (PBC), formerly referred to as primary biliary cirrhosis, is an infrequent progressive intrahepatic cholestatic autoimmune illness that can evolve into hepatic fibrosis, hepatic cirrhosis, hepatic failure, and, in some cases, hepatocellular carcinoma. The disease itself is characterized by T-lymphocyte-mediated chronic non-suppurative destructive cholangitis and elevated serum levels of extremely specific anti-mitochondrial autoantibodies (AMAs). In this article, we will not only review epidemiology, risk factors, natural history, predictive scores, radiologic approaches (e.g., acoustic radiation force impulse imaging, vibration controlled transient elastography, and magnetic resonance elastography), clinical features, serological characteristics covering biochemical markers, immunoglobulins, infections markers, biomarkers, predictive fibrosis marker, specific antibodies (including AMAs such as AMA-M2), anti-nuclear autoantibodies [such as anti-multiple nuclear dot autoantibodies (anti-sp100, PML, NDP52, anti-sp140), anti-rim-like/membranous anti-nuclear autoantibodies (anti-gp210, anti-p62), anti-centromere autoantibodies, and some of the novel autoantibodies], histopathological characteristics of PBC, diagnostic advances, and anti-diastole of PBC. Furthermore, this review emphasizes the recent advances in research of PBC in terms of therapies, including ursodeoxycholic acid, budesonide, methotrexate, obeticholic acid, cyclosporine A, fibrates such as bezafibrate and fenofibrate, rituximab, mesenchymal stem cells transplant, and hepatic transplant. Currently, hepatic transplant remains the only optimal choice with acknowledged treatment efficiency for end-stage PBC patients.
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Abstract
Alcohol consumption is often a comorbid condition in other chronic liver diseases. It has been shown to act in synergy to increase liver injury in viral hepatitis, hereditary hemochromatosis, and nonalcoholic fatty liver disease (NAFLD), leading to an increased risk of cirrhosis, hepatocellular carcinoma, and liver-related mortality. Data suggest that modest alcohol consumption may be inversely related to the risk of developing NAFLD and lower rates of progression of NAFLD to nonalcoholic steatohepatitis (NASH). This article reviews data on the relationship between alcohol consumption and other chronic liver diseases.
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Affiliation(s)
- Christine C Hsu
- Division of Gastroenterology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19146, USA
| | - Kris V Kowdley
- Swedish Liver Care Network, Swedish Medical Center, 1124 Columbia Street, Suite 600, Seattle, WA 98104, USA.
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30
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Zhang HC, Hu RF, Zhu T, Tong L, Zhang QQ. Primary biliary cirrhosis degree assessment by acoustic radiation force impulse imaging and hepatic fibrosis indicators. World J Gastroenterol 2016; 22:5276-5284. [PMID: 27298571 PMCID: PMC4893475 DOI: 10.3748/wjg.v22.i22.5276] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2016] [Revised: 03/02/2016] [Accepted: 03/30/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the assessment of primary biliary cirrhosis degree by acoustic radiation force impulse imaging (ARFI) and hepatic fibrosis indicators.
METHODS: One hundred and twenty patients who developed liver cirrhosis secondary to primary biliary cirrhosis were selected as the observation group, with the degree of patient liver cirrhosis graded by Child-Pugh (CP) score. Sixty healthy individuals were selected as the control group. The four indicators of hepatic fibrosis were detected in all research objects, including hyaluronic acid (HA), laminin (LN), type III collagen (PC III), and type IV collagen (IV-C). The liver parenchyma hardness value (LS) was then measured by ARFI technique. LS and the four indicators of liver fibrosis (HA, LN, PC III, and IV-C) were observed in different grade CP scores. The diagnostic value of LS and the four indicators of liver fibrosis in determining liver cirrhosis degree with PBC, whether used alone or in combination, were analyzed by receiver operating characteristic (ROC) curve.
RESULTS: LS and the four indicators of liver fibrosis within the three classes (A, B, and C) of CP scores in the observation group were higher than in the control group, with C class > B class > A class; the differences were statistically significant (P < 0.01). Although AUC values of LS within the three classes of CP scores were higher than in the four indicators of liver fibrosis, sensitivity and specificity were unstable. The ROC curves of LS combined with the four indicators of liver fibrosis revealed that: AUC and sensitivity in all indicators combined in the A class of CP score were higher than in LS alone, albeit with slightly decreased specificity; AUC and specificity in all indicators combined in the B class of CP score were higher than in LS alone, with unchanged sensitivity; AUC values (0.967), sensitivity (97.4%), and specificity (90%) of all indicators combined in the C class of CP score were higher than in LS alone (0.936, 92.1%, 83.3%).
CONCLUSION: The diagnostic value of PBC cirrhosis degree in liver cirrhosis degree assessment by ARFI combined with the four indicators of serum liver fibrosis is of satisfactory effectiveness and has important clinical application value.
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31
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Huang Q, Chu S, Yin X, Yu X, Kang C, Li X, Qiu Y. Interleukin-17A-Induced Epithelial-Mesenchymal Transition of Human Intrahepatic Biliary Epithelial Cells: Implications for Primary Biliary Cirrhosis. TOHOKU J EXP MED 2016; 240:269-275. [DOI: 10.1620/tjem.240.269] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Affiliation(s)
- Qingshui Huang
- Laboratory Medicine Center, Nanfang Hospital, Southern Medical University
- Clinical Laboratory, First Affiliated Hospital of Nanchang University
| | - Shuai Chu
- Laboratory Medicine Center, Nanfang Hospital, Southern Medical University
| | - Xiaofeng Yin
- Laboratory Medicine Center, Nanfang Hospital, Southern Medical University
| | - Xiaobin Yu
- Laboratory Medicine Center, Nanfang Hospital, Southern Medical University
| | - Chunmin Kang
- Laboratory Medicine Center, Nanfang Hospital, Southern Medical University
| | - Xin Li
- Laboratory Medicine Center, Nanfang Hospital, Southern Medical University
| | - Yurong Qiu
- Laboratory Medicine Center, Nanfang Hospital, Southern Medical University
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