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Cheng Y, Song Z, Liu Y, Xu X, Zhang D, Zou Y, Liu L, Zeng Y, Li W, Bai D, Dai D. Common molecular basis for MASH and hepatitis C revealed via systems biology approach. Front Oncol 2024; 14:1442221. [PMID: 39605886 PMCID: PMC11599856 DOI: 10.3389/fonc.2024.1442221] [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: 06/01/2024] [Accepted: 10/16/2024] [Indexed: 11/29/2024] Open
Abstract
Background Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by liver inflammation and damage caused by a buildup of fat in the liver. Hepatitis C, caused by hepatitis C virus (HCV), is a disease that can lead to liver cirrhosis, liver cancer, and liver failure. MASH and hepatitis C are the common causes of liver cirrhosis and hepatocellular carcinoma. Several studies have shown that hepatic steatosis is also a common histological feature of liver in HCV infected patients. However, the common molecular basis for MASH and hepatitis C remains poorly understood. Methods Firstly, differentially expressed genes (DEGs) for MASH and hepatitis C were extracted from the GSE89632, GSE164760 and GSE14323 datasets. Subsequently, the common DEGs shared among these datasets were determined using the Venn diagram. Next, a protein-protein interaction (PPI) network was constructed based on the common DEGs and the hub genes were extracted. Then, gene ontology (GO) and pathway analysis of the common DEGs were performed. Furthermore, transcription factors (TFs) and miRNAs regulatory networks were constructed, and drug candidates were identified. After the MASH and hepatitis C cell model was treated with predicted drug, the expression levels of the signature genes were measured by qRT-PCR and ELISA. Results 866 common DEGs were identified in MASH and hepatitis C. The GO analysis showed that the most significantly enriched biological process of the DEGs was the positive regulation of cytokine production. 10 hub genes, including STAT1, CCL2, ITGAM, PTPRC, CXCL9, IL15, SELL, VCAM1, TLR4 and CCL5, were selected from the PPI network. By constructing the TF-gene and miRNA-gene network, most prominent TFs and miRNAs were screened out. Potential drugs screening shows that Budesonide and Dinoprostone may benefit patients, and cellular experiments showed that Budesonide effectively inhibited the expression of genes related to glycolipid metabolism, fibrosis, and inflammatory factors. Conclusion We extracted 10 hub genes between MASH and hepatitis C, and performed a series of analyses on the genes. Molecular docking and in vitro studies have revealed that Budesonide can effectively suppress the progression of MASH and hepatitis C. This study can provide novel insights into the potential drug targets and biomarkers for MASH and hepatitis C.
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Affiliation(s)
- Yongwei Cheng
- Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Endoscopy Center and Gastroenterology Department, Shenzhen Children’s Hospital, Shenzhen, China
| | - Zihao Song
- GMU-GIBH Joint School of Life Sciences, The Guangdong-Hong Kong-Macao Joint Laboratory for Cell Fate Regulation and Diseases, Guangzhou Medical University, Guangzhou, China
| | - Ye Liu
- School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan, China
| | - Xichao Xu
- Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Endoscopy Center and Gastroenterology Department, Shenzhen Children’s Hospital, Shenzhen, China
| | - Dali Zhang
- Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Endoscopy Center and Gastroenterology Department, Shenzhen Children’s Hospital, Shenzhen, China
| | - Yigui Zou
- Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Endoscopy Center and Gastroenterology Department, Shenzhen Children’s Hospital, Shenzhen, China
| | - Liang Liu
- Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Endoscopy Center and Gastroenterology Department, Shenzhen Children’s Hospital, Shenzhen, China
| | - Yinzhen Zeng
- Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Endoscopy Center and Gastroenterology Department, Shenzhen Children’s Hospital, Shenzhen, China
| | - Wenwen Li
- Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Endoscopy Center and Gastroenterology Department, Shenzhen Children’s Hospital, Shenzhen, China
| | - Daming Bai
- Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Endoscopy Center and Gastroenterology Department, Shenzhen Children’s Hospital, Shenzhen, China
| | - Dongling Dai
- Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Endoscopy Center and Gastroenterology Department, Shenzhen Children’s Hospital, Shenzhen, China
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Mita E, Liu LJ, Shing D, Force L, Aoki K, Nakamoto D, Ishizaki A, Konishi H, Mizutani H, Ng LJ. Real-world Safety and Effectiveness of 24-week Sofosbuvir and Ribavirin Treatment in Patients Infected with Rare Chronic Hepatitis C Virus Genotypes 3, 4, 5, or 6 in Japan. Intern Med 2022; 62:1405-1414. [PMID: 36047126 DOI: 10.2169/internalmedicine.0067-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Objectives Real-world evidence on the safety and effectiveness of direct-acting antivirals in patients infected with chronic hepatitis C virus (HCV) genotypes (GTs) 3, 4, 5, or 6 in Japan is limited. This prospective observational study assesses the real-world safety profile and treatment effectiveness among patients prescribed sofosbuvir with ribavirin (SOF+RBV) for HCV GT3-6 infection in Japan. Methods Adults receiving 24-week SOF+RBV treatment for HCV GT3-6 infection were prospectively enrolled and observed through 24 weeks post-treatment for treatment-emergent adverse events (AEs) considered related to SOF and/or RBV by treating physicians and for a sustained virologic response at 12 and 24 weeks post-treatment (SVR12, SVR24). Incidence rates of related AEs and serious AEs (SAEs) were calculated. Proportions of patients experiencing related AEs/SAEs and those achieving SVR12 and SVR24 were assessed overall and by baseline characteristics, including treatment experience and cirrhosis status. Results Among the 50 patients included in the safety analysis, 92% had GT3 infection. The incidence rates of related AEs and SAEs were low overall (1.52 and 0.25 per 100 person-weeks, respectively), with 6.0% and 14.0% patients experiencing AEs related to SOF or RBV, respectively. There were no marked differences in the occurrence of related AEs/SAEs by patient baseline characteristics. SVR12 and SVR24 were achieved in 83.7% (41/49) and 82.2% (37/45) of patients, respectively. Lower effectiveness was observed among treatment-experienced patients and patients with cirrhosis at baseline. Conclusions This study demonstrated that SOF+RBV treatment for HCV GT3-6 infection was safe, effective, and an important treatment option for this difficult-to-treat patient population in Japan.
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Affiliation(s)
- Eiji Mita
- National Hospital Organization Osaka National Hospital, Japan
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Squamous Cell Carcinoma Antigen: Clinical Application and Research Status. Diagnostics (Basel) 2022; 12:diagnostics12051065. [PMID: 35626221 PMCID: PMC9139199 DOI: 10.3390/diagnostics12051065] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 04/21/2022] [Accepted: 04/22/2022] [Indexed: 02/04/2023] Open
Abstract
The squamous cell carcinoma antigen (SCCA) is a tumor marker that has gained increasing attention for its biological functions and significance in normal physiological and pathological processes. Not only SCCA but also circulating immune complexes of SCCA and immunoglobulin M (IgM) are involved in normal physiological and pathological processes, providing a background for numerous clinical studies aimed at assessing the potential role of SCCA, SCCA–IgM, and SCCA isoform complexes in clinical practice. Previous studies support the clinical value of SCCA as a tumor marker for either diagnosing squamous cancers or monitoring the response to radiotherapy or chemotherapy, tumor relapse, and treatment failure. However, these studies show contrasting results, making the diagnostic or prognostic value of SCCA controversial. To reduce clinical heterogeneity across studies and achieve a more accurate and reliable comparison of results, a standardized detection method, scoring system, and cutoff level need to be established. Moreover, despite the fact that performances of different methods are comparable, the dynamic observation of tumor marker kinetics should be conducted under the same method.
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Gil-Gómez A, Rojas Á, Liu CH, Gallego-Duran R, Muñoz-Hernandez R, Fassina G, Pontisso P, Ampuero J, Romero-Gómez M. Combination of squamous cell carcinoma antigen immunocomplex and alpha-fetoprotein in mid- and long-term prediction of hepatocellular carcinoma among cirrhotic patients. World J Gastroenterol 2021; 27:8343-8356. [PMID: 35068873 PMCID: PMC8717022 DOI: 10.3748/wjg.v27.i48.8343] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 06/27/2021] [Accepted: 12/10/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The combination of alpha-fetoprotein (AFP) and squamous cell carcinoma antigen immunocomplex (SCCA-IgM) have been proposed for its use in the screening of hepatocellular carcinoma (HCC). Current screening programs for all cirrhotic patients are controversial and a personalized screening is an unmet need in the precision medicine era.
AIM To determine the role of the combination of SCCA-IgM and AFP in predicting mid- and long-term appearance of HCC.
METHODS Two-hundred and three cirrhotic patients (Child A 74.9%, B 21.2%, C 3.9%) were followed-up prospectively every six months to screen HCC by ultrasound and AFP according to European Association for the Study of the Liver guidelines. The estimation cohort was recruited in Italy (30.5%; 62/203) and validation cohort from Spain (69.5%; 141/203). Patients underwent to evaluate SCCA-IgM by enzyme-linked immunosorbent assay (Hepa-IC, Xeptagen, Italy) and AFP levels at baseline. Patients were followed-up for 60 mo, being censored at the time of the appearance of HCC.
RESULTS There were 10.8% and 23.1% of HCC development at two- and five-years follow-up. Patients with HCC showed higher levels of SCCA-IgM than those without it (425.72 ± 568.33 AU/mL vs 195.93 ± 188.40 AU/mL, P = 0.009) during the five-year follow-up. In multivariate analysis, after adjusting by age, sex, aspartate transaminase and Child-Pugh, the following factors were independently associated with HCC: SCCA-IgM [Hazard ratio (HR) = 1.001, 95%CI: 1.000-1.002; P = 0.003], AFP (HR = 1.028, 95%CI: 1.009-1.046; P = 0.003) and creatinine (HR = 1.564 95%CI: 1.151-2.124; P = 0.004). The log-rank test of the combination resulted in 7.488 (P = 0.024) in estimation cohort and 11.061 (P = 0.004) in the validation cohort, and a 100% of correctly classified rate identifying a low-risk group in both cohorts in the two-year follow-up.
CONCLUSION We have constructed a predictive model based on the combination of SCCA-IgM and AFP that provides a new HCC screening method, which could be followed by tailored HCC surveillance for individual patients, especially for those cirrhotic patients belonging to the subgroup identified as low-risk of HCC development.
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Affiliation(s)
- Antonio Gil-Gómez
- SeLiver Group, Institute of Biomedicine of Seville, Seville 41013, Spain
- CIBERehd, Instituto de Salud Carlos III, Madrid 28029, Spain
- Mucosal Immunity Lab, IRCCS Humanitas Research Hospital, Milan 20089, Italy
| | - Ángela Rojas
- SeLiver Group, Institute of Biomedicine of Seville, Seville 41013, Spain
- CIBERehd, Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Chang-Hai Liu
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610017, Sichuan Province, China
- State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Chengdu 610017, Sichuan Province, China
| | - Rocio Gallego-Duran
- SeLiver Group, Institute of Biomedicine of Seville, Seville 41013, Spain
- CIBERehd, Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Rocio Muñoz-Hernandez
- SeLiver Group, Institute of Biomedicine of Seville, Seville 41013, Spain
- CIBERehd, Instituto de Salud Carlos III, Madrid 28029, Spain
| | | | - Patrizia Pontisso
- Department of Clinical and Experimental Medicine, University of Padova, Padova 35123, Italy
| | - Javier Ampuero
- SeLiver Group, Institute of Biomedicine of Seville, Seville 41013, Spain
- CIBERehd, Instituto de Salud Carlos III, Madrid 28029, Spain
- UCM Digestive Diseases, Virgen del Rocío University Hospital, Seville 41014, Spain
| | - Manuel Romero-Gómez
- SeLiver Group, Institute of Biomedicine of Seville, Seville 41013, Spain
- CIBERehd, Instituto de Salud Carlos III, Madrid 28029, Spain
- UCM Digestive Diseases, Virgen del Rocío University Hospital, Seville 41014, Spain
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Bettini S, Bordigato E, Milan G, Dal Pra' C, Favaretto F, Belligoli A, Sanna M, Serra R, Foletto M, Prevedello L, Busetto L, Fassina G, Vettor R, Fabris R. SCCA-IgM as a Potential Biomarker of Non-Alcoholic Fatty Liver Disease in Patients with Obesity, Prediabetes and Diabetes Undergoing Sleeve Gastrectomy. Obes Facts 2019; 12:291-306. [PMID: 31104052 PMCID: PMC6696770 DOI: 10.1159/000499717] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Accepted: 03/16/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) has a high prevalence in obesity and its presence should be screened. Laparoscopic sleeve gastrectomy (LSG) is an effective treatment for obesity, but its effects on NAFLD are still to be firmly established. The diagnosis of non-alcoholic steatohepatitis (NASH) is currently performed by liver biopsy, a costly and invasive procedure. Squamous cell carcinoma antigen-IgM (SCCA-IgM) is a biomarker of viral hepatitis to hepatocellular carcinoma development and its role in NAFLD to NASH progression has not yet been investigated. OBJECTIVE The aim of this study was to evaluate SCCA-IgM as a non-invasive biomarker of NAFLD/NASH in patients with different degrees of metabolic-complicated obesity before and after LSG. METHOD Fifty-six patients with obesity were studied before and 12 months after LSG; anthropometric, biochemical, clinical, and imaging data were collected. RESULTS At baseline steatosis was strongly associated with the glycaemic profile (p = 0.016) and was already present in prediabetic patients with obesity (82%). Only 3 patients had an SCCA-IgM level above the normal cut-off. SCCA-IgM titre did not change according to glycaemic profile or steatosis. Metabolic and inflammatory factors and transaminases significantly reduced after LSG-induced weight loss, except for SCCA-IgM. The ALT/AST ratio decreased post-LSG correlated with BMI (r = 0.297, p = 0.031), insulin (r = 0.354, p = 0.014), and triglycerides (r = 0.355, p = 0.009) reduction. CONCLUSIONS Our results confirm the tight link between NAFLD and metabolic complications, suggesting prediabetes as a new risk factor of steatosis. SCCA-IgM does not seem to have a role in the identification and prognosis of NAFLD.
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MESH Headings
- Adult
- Antigens, Neoplasm/blood
- Antigens, Neoplasm/immunology
- Biomarkers/blood
- Diabetes Mellitus, Type 2/blood
- Diabetes Mellitus, Type 2/complications
- Diabetes Mellitus, Type 2/diagnosis
- Diabetes Mellitus, Type 2/surgery
- Female
- Follow-Up Studies
- Gastrectomy/methods
- Gastrectomy/rehabilitation
- Humans
- Immunoglobulin M/blood
- Male
- Middle Aged
- Non-alcoholic Fatty Liver Disease/blood
- Non-alcoholic Fatty Liver Disease/complications
- Non-alcoholic Fatty Liver Disease/diagnosis
- Non-alcoholic Fatty Liver Disease/surgery
- Obesity/blood
- Obesity/complications
- Obesity/diagnosis
- Obesity/surgery
- Obesity, Morbid/blood
- Obesity, Morbid/complications
- Obesity, Morbid/diagnosis
- Obesity, Morbid/surgery
- Prediabetic State/blood
- Prediabetic State/complications
- Prediabetic State/diagnosis
- Prediabetic State/surgery
- Prognosis
- Risk Factors
- Serpins/blood
- Serpins/immunology
- Treatment Outcome
- Weight Loss
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Affiliation(s)
- Silvia Bettini
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy,
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy,
| | - Emanuel Bordigato
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy
| | - Gabriella Milan
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy
| | - Chiara Dal Pra'
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy
| | - Francesca Favaretto
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy
| | - Anna Belligoli
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy
| | - Marta Sanna
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy
| | - Roberto Serra
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy
| | - Mirto Foletto
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy
| | - Luca Prevedello
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy
| | - Luca Busetto
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy
| | | | - Roberto Vettor
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy
| | - Roberto Fabris
- Center for the Study and Integrated Treatment of Obesity, University Hospital of Padua, Padua, Italy
- Internal Medicine 3, Department of Medicine, University Hospital of Padua, Padua, Italy
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Liu CH, Gil-Gómez A, Ampuero J, Romero-Gómez M. Diagnostic accuracy of SCCA and SCCA-IgM for hepatocellular carcinoma: A meta-analysis. Liver Int 2018; 38:1820-1831. [PMID: 29704434 DOI: 10.1111/liv.13867] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2017] [Accepted: 04/14/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Squamous cell carcinoma antigen (SCCA) and its immune complex (SCCA-IgM) have been proposed for use in the screening of hepatocellular carcinoma (HCC). We conducted a meta-analysis to evaluate the diagnostic performance of SCCA and SCCA-IgM and of both combined with alpha-foetoprotein. METHODS After a systematic review of the relevant studies, the sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio (DOR) and area under curve (AUC) for the diagnosis of HCC were pooled using bivariate meta-analysis. Hierarchic summary receiver operating characteristic curves were used to summarize the overall test performance. Bivariate boxplots were used to confirm whether the threshold effect existed. A Fagan nomogram was used to assess the clinical utility. Heterogeneity was explored by sensitivity analysis, univariable meta-regression and subgroup analysis. RESULTS Eleven studies that had HCC diagnosis as their purpose were ultimately included in the quantitative analysis. The summary estimates were as follows: SCCA (AUC: 0.80 [95% CI: 0.76-0.83]) and SCCA-IgM (AUC: 0.77 [95% CI: 0.74-0.83]) demonstrated similar diagnostic performance, while a combination of AFP and SCCA-IgM had an AUC of 0.90 (95% CI: 0.87-0.92) and a DOR of 22.87 (95% CI: 8.38-62.40). Meta-regression showed that patient selection, cut-off values, reference standards and tumour biopsy as the diagnostic method significantly influenced the heterogeneity of the included studies. CONCLUSIONS Both SCCA and SCCA-IgM showed a moderate diagnostic accuracy for HCC screening; the combination of SCCA-IgM and AFP is the best diagnostic option.
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Affiliation(s)
- Chang-Hai Liu
- Institute of Biomedicine of Seville, Seville, Spain.,University of Seville, Seville, Spain
| | | | - Javier Ampuero
- Institute of Biomedicine of Seville, Seville, Spain.,University of Seville, Seville, Spain.,Unit for the Clinical Management of Digestive Diseases and CIBERehd, University Hospital Virgen del Rocío, Seville, Spain
| | - Manuel Romero-Gómez
- Institute of Biomedicine of Seville, Seville, Spain.,University of Seville, Seville, Spain.,Unit for the Clinical Management of Digestive Diseases and CIBERehd, University Hospital Virgen del Rocío, Seville, Spain
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Gallotta A, Paneghetti L, Mrázová V, Bednárová A, Kružlicová D, Frecer V, Miertus S, Biasiolo A, Martini A, Pontisso P, Fassina G. Development of a novel diagnostic algorithm to predict NASH in HCV-positive patients. Int J Biol Markers 2018; 33:231-236. [PMID: 29712495 DOI: 10.1177/1724600817753577] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Non-alcoholic steato-hepatitis (NASH) is a severe disease characterised by liver inflammation and progressive hepatic fibrosis, which may progress to cirrhosis and hepatocellular carcinoma. Clinical evidence suggests that in hepatitis C virus patients steatosis and NASH are associated with faster fibrosis progression and hepatocellular carcinoma. A safe and reliable non-invasive diagnostic method to detect NASH at its early stages is still needed to prevent progression of the disease. We prospectively enrolled 91 hepatitis C virus-positive patients with histologically proven chronic liver disease: 77 patients were included in our study; of these, 10 had NASH. For each patient, various clinical and serological variables were collected. Different algorithms combining squamous cell carcinoma antigen-immunoglobulin-M (SCCA-IgM) levels with other common clinical data were created to provide the probability of having NASH. Our analysis revealed a statistically significant correlation between the histological presence of NASH and SCCA-IgM, insulin, homeostasis model assessment, haemoglobin, high-density lipoprotein and ferritin levels, and smoke. Compared to the use of a single marker, algorithms that combined four, six or seven variables identified NASH with higher accuracy. The best diagnostic performance was obtained with the logistic regression combination, which included all seven variables correlated with NASH. The combination of SCCA-IgM with common clinical data shows promising diagnostic performance for the detection of NASH in hepatitis C virus patients.
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Affiliation(s)
| | | | - Viera Mrázová
- 2 Faculty of Natural Sciences, University of SS. Cyril & Methodius - Slovakia
| | - Adriana Bednárová
- 2 Faculty of Natural Sciences, University of SS. Cyril & Methodius - Slovakia
| | - Dáša Kružlicová
- 2 Faculty of Natural Sciences, University of SS. Cyril & Methodius - Slovakia
| | - Vladimir Frecer
- 3 International Centre for Applied Research and Sustainable Technology - Slovakia.,4 Department of Physical Chemistry of Drugs, Comenius University - Slovakia
| | - Stanislav Miertus
- 2 Faculty of Natural Sciences, University of SS. Cyril & Methodius - Slovakia.,3 International Centre for Applied Research and Sustainable Technology - Slovakia
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Bui Huu H, Ha Thuc N, Thi Le HP, Thi Thanh TD, Luong Bac A, Tiribelli C, Pontisso P, Gallotta A, Paneghetti L, Fassina G. Characterization of SCCA-IgM as a biomarker of liver disease in an Asian cohort of patients. Scandinavian Journal of Clinical and Laboratory Investigation 2018; 78:204-210. [PMID: 29381084 DOI: 10.1080/00365513.2018.1432072] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Viral hepatitis infection is a major global issue and a leading cause of liver disease and associated deaths. Over time, patients infected with hepatitis B (HBV) or C virus (HCV) develop cirrhosis and, eventually, hepatocellular carcinoma (HCC). For this reason, they need to be constantly monitored. Current Asian guidelines recommend the determination of serum alpha-fetoprotein (AFP) together with liver ultrasounds every six months to detect HCC nodules. However, both methods have several limitations, and other biomarkers have been studied for monitoring cirrhosis, including SCCA-IgM, an immune-complex formed by Squamous Cell Carcinoma Antigen and IgM. To date, SCCA-IgM has been validated as a novel biomarker for liver diseases only in European populations. The aim of our study was to analyze SCCA-IgM as a biomarker to monitor cirrhosis evolution in an Asian cohort of patients and to compare its performance to that of AFP. We analyzed the concentration of AFP and SCCA-IgM in serum samples obtained from a group of Asian adult patients with cirrhosis or HCC and a control group of patients admitted for gastrointestinal disorders. In untreated patients and similarly to AFP, SCCA-IgM levels were significantly higher in patients with cirrhosis compared to those with HCC. In addition, SCCA-IgM, but not AFP serological levels, were significantly lower in HCC patients who were treated with surgical resection compared to those who received a different therapy.
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Affiliation(s)
- Hoang Bui Huu
- a University of Medicine and Pharmacy of Ho Chi Minh , Ho Chi Minh City , Vietnam
| | - Nhuong Ha Thuc
- a University of Medicine and Pharmacy of Ho Chi Minh , Ho Chi Minh City , Vietnam
| | - Hoa Pham Thi Le
- a University of Medicine and Pharmacy of Ho Chi Minh , Ho Chi Minh City , Vietnam
| | - Thuy Do Thi Thanh
- a University of Medicine and Pharmacy of Ho Chi Minh , Ho Chi Minh City , Vietnam
| | - An Luong Bac
- a University of Medicine and Pharmacy of Ho Chi Minh , Ho Chi Minh City , Vietnam
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9
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Biasiolo A, Trotta E, Fasolato S, Ruvoletto M, Martini A, Gallotta A, Fassina G, Angeli P, Gatta A, Pontisso P. Squamous cell carcinoma antigen-IgM is associated with hepatocellular carcinoma in patients with cirrhosis: A prospective study. Dig Liver Dis 2016; 48:197-202. [PMID: 26614642 DOI: 10.1016/j.dld.2015.10.022] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2015] [Revised: 09/29/2015] [Accepted: 10/23/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Squamous cell carcinoma antigen (SCCA)-IgM complex has been described as a promising tool to identify patients with progressive liver disease at higher risk of hepatocellular carcinoma (HCC) development in retrospective studies. AIM To assess the clinical value of this biomarker in patients with cirrhosis in a prospective study. METHODS Patients with overt cirrhosis were prospectively evaluated at 6-month intervals for HCC development and decompensation with clinical examination, liver ultrasound, α-fetoprotein measurement. SCCA-IgM was measured in serum by immunoenzymatic assay. Median follow-up duration was 52 months (range 12-68 months). RESULTS 70 patients (26% male; mean age 56±10 years) were enrolled. The main aetiological factors were alcohol (44%) and hepatitis C (34%). Baseline values of SCCA-IgM were significantly higher in patients who developed HCC. Positivity of the biomarker at baseline was associated with a significantly shorter HCC-free survival, while α-fetoprotein (cut off >20 ng/ml) was not significant. SCCA-IgM positivity and hepatitis C were significant prognostic factors for HCC development. The biomarker was not associated with the development of clinical complications of cirrhosis. CONCLUSION This prospective study demonstrates that in patients with cirrhosis SCCA-IgM is associated with HCC development and may be useful for clinical management of cirrhotic patients at higher risk of HCC development.
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Affiliation(s)
| | - Elisa Trotta
- Department of Medicine, University of Padua, Italy
| | | | | | | | | | | | - Paolo Angeli
- Department of Medicine, University of Padua, Italy
| | - Angelo Gatta
- Department of Medicine, University of Padua, Italy
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Martini A, Gallotta A, Pontisso P, Fassina G. Clinical applications of squamous cell carcinoma antigen-immunoglobulins M to monitor chronic hepatitis C. World J Hepatol 2015; 7:2913-2919. [PMID: 26689503 PMCID: PMC4678378 DOI: 10.4254/wjh.v7.i29.2913] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2015] [Revised: 09/30/2015] [Accepted: 12/02/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) is the main cause of chronic liver disease and cirrhosis in Western countries. Over time, the majority of cirrhotic patients develop hepatocellular carcinoma (HCC), one of the most common fatal cancers worldwide - fourth for incidence rate. A high public health priority need is the development of biomarkers to screen for liver disease progression and for early diagnosis of HCC development, particularly in the high risk population represented by HCV-positive patients with cirrhosis. Several studies have shown that serological determination of a novel biomarker, squamous cell carcinoma antigen-immunoglobulins M (SCCA-IgM), might be useful to identify patients with progressive liver disease. In the initial part of this review we summarize the main clinical studies that have investigated this new circulating biomarker on HCV-infected patients, providing evidence that in chronic hepatitis C SCCA-IgM may be used to monitor progression of liver disease, and also to assess the virological response to antiviral treatment. In the last part of this review we address other, not less important, clinical applications of this biomarker in hepatology.
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Biasiolo A, Martini A, Pontisso P. New biomarkers for clinical management of hepatitis C virus infected patients. World J Clin Infect Dis 2015; 5:59-66. [DOI: 10.5495/wjcid.v5.i4.59] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2015] [Revised: 08/28/2015] [Accepted: 10/19/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the third most frequent oncological cause of death worldwide, principally a consequence of hepatitis C virus (HCV) infection and its prognosis is mostly poor. For early identification and surveillance of HCV patients with liver disease progression, the availability of suitable diagnostic and prognostic biomarkers is still an unmet clinical need. Alfa-fetoprotein together with imaging techniques is commonly used, however its specificity and sensitivity are not satisfactory. Several clinical and serological data have been proposed to define the risk of disease progression in HCV infected patients and new biomarkers have been proposed, including post-transcriptionally modified molecules and genetic biomarkers. The present editorial article attempts to summarize the current knowledge on the new promising tools for effective early diagnosis of HCV-related liver disease progression and for the surveillance of HCC.
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