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Albarrak J, Al-Shamsi H. Current Status of Management of Hepatocellular Carcinoma in The Gulf Region: Challenges and Recommendations. Cancers (Basel) 2023; 15:cancers15072001. [PMID: 37046662 PMCID: PMC10093592 DOI: 10.3390/cancers15072001] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 03/23/2023] [Accepted: 03/25/2023] [Indexed: 03/30/2023] Open
Abstract
The burden of hepatocellular carcinoma (HCC) is on the rise in the Gulf region, with most patients being diagnosed in the intermediate or advanced stages. Surgery is a treatment option for only a few, and the majority of patients receive either locoregional treatment (percutaneous ethanol injection, radiofrequency ablation, transarterial chemoembolization [TACE], radioembolization, radiotherapy, or transarterial radioembolization) or systemic therapy (for those ineligible for locoregional treatments or who do not benefit from TACE). The recent emergence of novel immunotherapies such as immune checkpoint inhibitors has begun to change the landscape of systemic HCC treatment in the Gulf. The combination of atezolizumab and bevacizumab is currently the preferred first-line therapy in patients not at risk of bleeding. Additionally, the HIMALAYA trial has demonstrated the superiority of the durvalumab plus tremelimumab combination (STRIDE regimen) therapy in efficacy and safety compared with sorafenib in patients with unresectable HCC. However, there is a lack of data on post-progression treatment after first-line therapy with either atezolizumab plus bevacizumab or durvalumab plus tremelimumab regimens, highlighting the need for better-designed studies for improved management of patients with unresectable HCC in the Gulf region.
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Affiliation(s)
- Jasem Albarrak
- Kuwait Cancer Control Center, Sabah Health Region, Kuwait City 8WF3+WR8, Kuwait;
| | - Humaid Al-Shamsi
- Burjeel Medical City- Burjeel Holding, Abu Dhabi 92510, United Arab Emirates
- College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
- Emirates Oncology Society, Dubai 22107, United Arab Emirates
- Correspondence:
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Wu SY, Chen WM, Chen YC, Chiang MF, Lee MC, Soong RS. Effects of H1-Antihistamines on hepatocellular carcinoma risk in patients with type 2 diabetes mellitus. DIABETES & METABOLISM 2023; 49:101393. [PMID: 36170945 DOI: 10.1016/j.diabet.2022.101393] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 09/18/2022] [Accepted: 09/19/2022] [Indexed: 01/28/2023]
Abstract
PURPOSE H1-antihistamines (AHs) may exert protective effects against cancer. We investigated the association of AH use with hepatocellular carcinoma (HCC) risk in type 2 diabetes mellitus (T2DM) patients without hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. METHODS The data of patients with T2DM enrolled from Taiwan's National Health Insurance Research Database were examined for the period of January 1, 2008, to December 31, 2018. We used the Kaplan-Meier method and Cox proportional hazards regression to evaluate the AH use-HCC risk association. RESULTS After 1:1 propensity score matching was performed, the two cohorts were each divided into AH users (n = 47,990) and nonusers (n = 47,990). The risk of HCC was significantly lower in AH users than in AH nonusers (adjusted hazard ratio [aHR]: 0.55 95% confidence interval [95% CI], 0.46 to 0.67; IRR: 0.70; 95% CI, 0.60 to 0.84), respectively. The dose-response relationship between AH use and HCC risk was also observed (aHRs: 0.58, 0.56, 0.50, and 0.41 for 28-35, 36-49, 50-77, and >77 cumulative defined daily doses of AH, respectively). CONCLUSION AH use can reduce HCC risk in T2DM patients without HBV or HCV infection in a dose-dependent manner.
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Affiliation(s)
- Szu-Yuan Wu
- 1Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, New Taipei City, Taiwan; Artificial Intelligence Development Center, Fu Jen Catholic University, New Taipei City, Taiwan; Department of Food Nutrition and Health Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan; Big Data Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan; Division of Radiation Oncology, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan; Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan; Centers for Regional Anesthesia and Pain Medicine, Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Wan-Ming Chen
- 1Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, New Taipei City, Taiwan; Artificial Intelligence Development Center, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Yi-Chan Chen
- Department of General Surgery, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Ming-Feng Chiang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan 265, Taiwan
| | - Ming-Che Lee
- Department of Surgery, Taipei Municipal Wanfang Hospital, Taipei, Taiwan; College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Ruey-Shyang Soong
- Department of Surgery, Taipei Municipal Wanfang Hospital, Taipei, Taiwan; College of Medicine, Taipei Medical University, Taipei, Taiwan.
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Lin W, Zhong H, Wen C, He Y, Zheng X, Li H, Chen X, He H, Chen J, Chen L, Liu C, Tang X, Cai W, Li L. Persistently low CD4 cell counts are associated with hepatic events in HCV/HIV coinfected patients: data from the national free antiretroviral treatment program of China. Chin Med J (Engl) 2022; 135:2699-2705. [PMID: 36574222 PMCID: PMC9943990 DOI: 10.1097/cm9.0000000000002502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Chronic liver disease has emerged as a leading cause of non-acquired immune deficiency syndrome (AIDS)-related mortality in hepatitis C virus (HCV)/human immunodeficiency virus (HIV)-coinfected patients. The relationship between CD4 cell count and HIV-related opportunistic infections and tumors has been well characterized; however, it is unclear whether CD4 cell count is associated with HCV-related hepatic events. METHODS This observational cohort study enrolled HCV/HIV-coinfected patients from the National Free Antiretroviral Treatment Program of China from 2004 to 2019 in Guangzhou. The primary outcome was a composite of hepatic events, including cirrhosis complications, hepatocellular carcinoma (HCC), and liver-related mortality. Kaplan-Meier survival and multivariate logistic regression analyses were performed. RESULTS Among the 793 patients, 43 developed hepatic events during a median follow-up of 6.7 years, including 35 cirrhosis complications, 13 HCC cases, and 14 cases of liver-related mortality. The 5-year and 10-year cumulative incidences of hepatic events were 4.2% and 9.3%, respectively. Patients who developed hepatic events had a less satisfactory increase in CD4 cell count, lower peak CD4 (354.5 cells/μL vs. 560.0 cells/μL, P < 0.001), and lower percentage of peak CD4 > 500 cells/μL (30.2% vs. 60.7%, P < 0.001) after the initiation of antiretroviral therapy (ART) than those who did not. The cumulative incidences of hepatic events were higher in patients with lower peak CD4 levels with adjusted odds ratios of 3.96 (95% confidence interval [CI]: 1.51-10.40), 2.25 (95% CI: 0.87-5.86), and 0.98 (95% CI: 0.35-2.74) for patients with peak CD4 at <200 cells/μL, 200-350 cells/μL, and 351 to 500 cells/μL, respectively, relative to those with peak CD4 > 500 cells/μL. Peak CD4 was negatively associated with the risk of hepatic events in a dose-response manner ( P -value for trend = 0.004). CONCLUSION Persistently low CD4 cell counts after ART are independently associated with a high risk of hepatic events in HCV/HIV-coinfected patients, highlighting the important role of immune reconstitution in improving liver outcomes.
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Affiliation(s)
- Weiyin Lin
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510060, China
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Di Ciaula A, Bonfrate L, Krawczyk M, Frühbeck G, Portincasa P. Synergistic and Detrimental Effects of Alcohol Intake on Progression of Liver Steatosis. Int J Mol Sci 2022; 23:2636. [PMID: 35269779 PMCID: PMC8910376 DOI: 10.3390/ijms23052636] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 02/24/2022] [Accepted: 02/25/2022] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are the most common liver disorders worldwide and the major causes of non-viral liver cirrhosis in the general population. In NAFLD, metabolic abnormalities, obesity, and metabolic syndrome are the driving factors for liver damage with no or minimal alcohol consumption. ALD refers to liver damage caused by excess alcohol intake in individuals drinking more than 5 to 10 daily units for years. Although NAFLD and ALD are nosologically considered two distinct entities, they show a continuum and exert synergistic effects on the progression toward liver cirrhosis. The current view is that low alcohol use might also increase the risk of advanced clinical liver disease in NAFLD, whereas metabolic factors increase the risk of cirrhosis among alcohol risk drinkers. Therefore, special interest is now addressed to individuals with metabolic abnormalities who consume small amounts of alcohol or who binge drink, for the role of light-to-moderate alcohol use in fibrosis progression and clinical severity of the liver disease. Evidence shows that in the presence of NAFLD, there is no liver-safe limit of alcohol intake. We discuss the epidemiological and clinical features of NAFLD/ALD, aspects of alcohol metabolism, and mechanisms of damage concerning steatosis, fibrosis, cumulative effects, and deleterious consequences which include hepatocellular carcinoma.
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Affiliation(s)
- Agostino Di Ciaula
- Clinica Medica “Augusto Murri”, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School—Piazza Giulio Cesare 11, 70124 Bari, Italy; (A.D.C.); (L.B.)
| | - Leonilde Bonfrate
- Clinica Medica “Augusto Murri”, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School—Piazza Giulio Cesare 11, 70124 Bari, Italy; (A.D.C.); (L.B.)
| | - Marcin Krawczyk
- Department of Medicine II Saarland University Medical Center, Saarland University, 66424 Homburg, Germany;
- Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Centre for Preclinical Research, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Gema Frühbeck
- Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, 31008 Pamplona, Spain;
- Metabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), ISCIII, 31009 Pamplona, Spain
- Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31009 Pamplona, Spain
| | - Piero Portincasa
- Clinica Medica “Augusto Murri”, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School—Piazza Giulio Cesare 11, 70124 Bari, Italy; (A.D.C.); (L.B.)
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Krapić M, Kavazović I, Wensveen FM. Immunological Mechanisms of Sickness Behavior in Viral Infection. Viruses 2021; 13:v13112245. [PMID: 34835051 PMCID: PMC8624889 DOI: 10.3390/v13112245] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 11/04/2021] [Indexed: 12/11/2022] Open
Abstract
Sickness behavior is the common denominator for a plethora of changes in normal behavioral routines and systemic metabolism during an infection. Typical symptoms include temperature, muscle weakness, and loss of appetite. Whereas we experience these changes as a pathology, in fact they are a carefully orchestrated response mediated by the immune system. Its purpose is to optimize immune cell functionality against pathogens whilst minimizing viral replication in infected cells. Sickness behavior is controlled at several levels, most notably by the central nervous system, but also by other organs that mediate systemic homeostasis, such as the liver and adipose tissue. Nevertheless, the changes mediated by these organs are ultimately initiated by immune cells, usually through local or systemic secretion of cytokines. The nature of infection determines which cytokine profile is induced by immune cells and therefore which sickness behavior ensues. In context of infection, sickness behavior is typically beneficial. However, inappropriate activation of the immune system may induce adverse aspects of sickness behavior. For example, tissue stress caused by obesity may result in chronic activation of the immune system, leading to lasting changes in systemic metabolism. Concurrently, metabolic disease prevents induction of appropriate sickness behavior following viral infection, thus impairing the normal immune response. In this article, we will revisit recent literature that elucidates both the benefits and the negative aspects of sickness behavior in context of viral infection.
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Clinical Presentation of Hepatocellular Carcinoma in African Americans vs. Caucasians: A Retrospective Analysis. PATHOPHYSIOLOGY 2021; 28:387-399. [PMID: 35366282 PMCID: PMC8830457 DOI: 10.3390/pathophysiology28030026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 08/10/2021] [Accepted: 08/19/2021] [Indexed: 12/27/2022] Open
Abstract
Hepatocellular carcinoma (HCC) remains an important form of cancer-related morbidity and mortality in the U.S. and worldwide. Previous U.S.-based studies on survival suggest ethnic disparities in HCC patients, but the complex interplay of multiple factors that contribute are still incompletely understood. Here we considered the influences of risk factors contributing towards HCC survival, including ethnic background, over ten years at a premier academic medical center with a majority (57.20%) African American (AA) population. Retrospective HCC data were collected from 2008–2018 at LSUHSC-Shreveport, an urban tertiary medical center. Data included demographics, comorbidities, liver disease characteristics, and tumor parameters. Statistical analysis was performed using Chi Square and one-way ANOVA. Results: 229 HCC patients were identified (male 78.6%). The mean HCC age at diagnosis was 61 years (SD = 7.3). Compared to non-Hispanic Caucasians (42.7%), AA patients (57.2% of total) were older at presentation, had more frequent diabetes/dyslipidemia/NAFLD (45 (34.3%) compared with 19 (19.3%) in non-Hispanic Caucasians, p = 0.02), and had a larger HCC burden at diagnosis. We conclude that compared to white patients, despite having similar BMI and MELD scores and rates of portal vein thrombosis, AA patients with HCC in our cohort were older at presentation, had a significantly increased incidence of modifiable metabolic risk factors including diabetes, higher AFP values, increased incidence of gallstones, and larger sized HCCs, and were more likely to be outside Milan criteria. These findings have important prognostic and diagnostic implications for developing a more targeted HCC surveillance program.
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Abstract
The immune and endocrine systems collectively control homeostasis in the body. The endocrine system ensures that values of essential factors and nutrients such as glucose, electrolytes and vitamins are maintained within threshold values. The immune system resolves local disruptions in tissue homeostasis, caused by pathogens or malfunctioning cells. The immediate goals of these two systems do not always align. The immune system benefits from optimal access to nutrients for itself and restriction of nutrient availability to all other organs to limit pathogen replication. The endocrine system aims to ensure optimal nutrient access for all organs, limited only by the nutrients stores that the body has available. The actual state of homeostatic parameters such as blood glucose levels represents a careful balance based on regulatory signals from the immune and endocrine systems. This state is not static but continuously adjusted in response to changes in the current metabolic needs of the body, the amount of resources it has available and the level of threats it encounters. This balance is maintained by the ability of the immune and endocrine systems to interact and co-regulate systemic metabolism. In context of metabolic disease, this system is disrupted, which impairs functionality of both systems. The failure of the endocrine system to retain levels of nutrients such as glucose within threshold values impairs functionality of the immune system. In addition, metabolic stress of organs in context of obesity is perceived by the immune system as a disruption in local homeostasis, which it tries to resolve by the excretion of factors which further disrupt normal metabolic control. In this chapter, we will discuss how the immune and endocrine systems interact under homeostatic conditions and during infection with a focus on blood glucose regulation. In addition, we will discuss how this system fails in the context of metabolic disease.
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8
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Shaaban A, Salamah R, Abo Elseud Y, Mohanty A, Albarrak J. Presentation and Outcomes of Hepatocellular Carcinoma in the Arabian Peninsula: A Review of a Single Institution Experience in the Sorafenib Era. J Gastrointest Cancer 2021; 52:85-89. [PMID: 31808059 DOI: 10.1007/s12029-019-00341-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
PURPOSE There is a growing evidence showing that there are geographic differences in hepatocellular carcinoma (HCC). Little is known about the characteristics of hepatocellular carcinoma in the Arabian Peninsula. The present study examines the presentation and outcomes of HCC in a single institution. METHODS A retrospective chart review of patients presented with advanced-stage HCC to Kuwait Cancer Control Center (KCCC) between 2008 and 2018 was conducted. Data collected included patients demographics, HCC risk factors, performance status, Child-Pugh score, pick up of sorafenib, and survival. RESULTS About 111 cases were analyzed. The mean age of the cohort was 61.8 ± 11.4 years and 94 patients (84.7%) were males. HCV and diabetes were the most common risk factors for HCC and presented in 60 patients (54.1%) and 45 patients (40.5%), respectively. About 78 (70.3%) patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 at presentation. Only 29 (26.1%) patients presented with Child-Pugh class A, while 42 (40.4%) patients received sorafenib. The median overall survival was only 3 months. CONCLUSIONS In our cohort, HCV and diabetes were the main risk factors for HCC. The majority of patients was not amenable to sorafenib treatment and carries a very poor prognosis.
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Affiliation(s)
- A Shaaban
- Kuwait Cancer Control Centre, Shuwaikh, Kuwait. .,Minia University Hospital, Menia Governorate, Egypt.
| | - R Salamah
- Kuwait Cancer Control Centre, Shuwaikh, Kuwait
| | | | - A Mohanty
- Kuwait Cancer Control Centre, Shuwaikh, Kuwait
| | - J Albarrak
- Kuwait Cancer Control Centre, Shuwaikh, Kuwait
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Dajti E, Alemanni LV, Marasco G, Montagnani M, Azzaroli F. Approaches to the Diagnosis of Portal Hypertension: Non-Invasive or Invasive Tests? Hepat Med 2021; 13:25-36. [PMID: 33776492 PMCID: PMC7987277 DOI: 10.2147/hmer.s278077] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Accepted: 02/19/2021] [Indexed: 12/15/2022] Open
Abstract
Portal hypertension is the main driver of complications in patients with advanced chronic liver disease (ACLD) and is defined by values of hepatic venous pressure gradient measurement (HVPG) >5 mmHg. Values of HVPG ≥10 mmHg determine the presence of clinically significant portal hypertension (CSPH), the main predictor of the risk of variceal bleeding, hepatic decompensation, and mortality. However, its measurement is invasive and requires high expertise, so its routine use outside third level centers or clinical trials is limited. In the last decades, several non-invasive tests (NITs) have been developed and validated for the diagnosis of portal hypertension. Among these, liver (LSM) and spleen stiffness measurement (SSM) are the most promising tools available, as they have been proven accurate to predict CSPH, high-risk esophageal varices, decompensation, and mortality in patients with ACLD. In the last Baveno VI Consensus proceedings, LSM evaluation was recommended for the first time for diagnosis of CSPH (LSM >20-25 kPa) and the screening of patients with a low probability of having high-risk varices (LSM <20 kPa and platelet count >150.000/mm3). In this review, we aimed to summarize the growing evidence supporting the use of non-invasive tests for the evaluation of portal hypertension in patients with chronic liver disease.
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Affiliation(s)
- Elton Dajti
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Luigina Vanessa Alemanni
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Giovanni Marasco
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Marco Montagnani
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Francesco Azzaroli
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
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Turk Wensveen T, Gašparini D, Rahelić D, Wensveen FM. Type 2 diabetes and viral infection; cause and effect of disease. Diabetes Res Clin Pract 2021; 172:108637. [PMID: 33352263 PMCID: PMC8050380 DOI: 10.1016/j.diabres.2020.108637] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 11/27/2020] [Accepted: 12/16/2020] [Indexed: 02/06/2023]
Abstract
The recent pandemic of COVID-19 has made abundantly clear that Type 2 diabetes (T2D) increases the risk of more frequent and more severe viral infections. At the same time, pro-inflammatory cytokines of an anti-viral Type-I profile promote insulin resistance and form a risk factor for development of T2D. What this illustrates is that there is a reciprocal, detrimental interaction between the immune and endocrine system in the context of T2D. Why these two systems would interact at all long remained unclear. Recent findings indicate that transient changes in systemic metabolism are induced by the immune system as a strategy against viral infection. In people with T2D, this system fails, thereby negatively impacting the antiviral immune response. In addition, immune-mediated changes in systemic metabolism upon infection may aggravate glycemic control in T2D. In this review, we will discuss recent literature that sheds more light on how T2D impairs immune responses to viral infection and how virus-induced activation of the immune system increases risk of development of T2D.
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Affiliation(s)
- Tamara Turk Wensveen
- Center for Diabetes, Endocrinology and Cardiometabolism, Thallassotherapia, Opatija, Croatia; Department of Endocrinology, Diabetes and Metabolic Disorders, Clinical Hospital Centre, Rijeka, Croatia; Department of Internal Medicine, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | - Dora Gašparini
- Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | - Dario Rahelić
- Vuk Vrhovac University Clinic for Diabetes, Endocrinology and Metabolic Diseases, Merkur University Hospital, Zagreb, Croatia; School of Medicine, University of Zagreb, Zagreb, Croatia; School of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Felix M Wensveen
- Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
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Marasco G, Colecchia A, Silva G, Rossini B, Eusebi LH, Ravaioli F, Dajti E, Alemanni LV, Colecchia L, Renzulli M, Golfieri R, Festi D. Non-invasive tests for the prediction of primary hepatocellular carcinoma. World J Gastroenterol 2020; 26:3326-3343. [PMID: 32655261 PMCID: PMC7327793 DOI: 10.3748/wjg.v26.i24.3326] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Revised: 04/08/2020] [Accepted: 06/12/2020] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world and it is one of the main complications of cirrhosis and portal hypertension. Even in the presence of a well-established follow-up protocol for cirrhotic patients, to date poor data are available on predictive markers for primary HCC occurrence in the setting of compensated advanced chronic liver disease patients (cACLD). The gold standard method to evaluate the prognosis of patients with cACLD, beyond liver fibrosis assessed with histology, is the measurement of the hepatic venous pressure gradient (HVPG). An HVPG ≥10 mmHg has been related to an increased risk of HCC in cACLD patients. However, these methods are burdened by additional costs and risks for patients and are mostly available only in referral centers. In the last decade increasing research has focused on the evaluation of several, simple, non-invasive tests (NITs) as predictors of HCC development. We reviewed the currently available literature on biochemical and ultrasound-based scores developed for the non-invasive evaluation of liver fibrosis and portal hypertension in predicting primary HCC. We found that the most reliable methods to assess HCC risk were the liver stiffness measurement, the aspartate aminotransferase to platelet ratio index score and the fibrosis-4 index. Other promising NITs need further investigations and validation for different liver disease aetiologies.
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Affiliation(s)
- Giovanni Marasco
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
| | - Antonio Colecchia
- Unit of Gastroenterology, Borgo Trento University Hospital of Verona, Verona 37126, Italy
| | - Giovanni Silva
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
| | - Benedetta Rossini
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
| | - Leonardo Henry Eusebi
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
| | - Federico Ravaioli
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
| | - Elton Dajti
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
| | - Luigina Vanessa Alemanni
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
| | - Luigi Colecchia
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
| | - Matteo Renzulli
- Radiology Unit, Sant’Orsola Malpighi Hospital, University of Bologna, Bologna 40138, Italy
| | - Rita Golfieri
- Radiology Unit, Sant’Orsola Malpighi Hospital, University of Bologna, Bologna 40138, Italy
| | - Davide Festi
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
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12
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HCV-Related Mortality Among HIV/HCV Co-infected Patients: The Importance of Behaviors in the HCV Cure Era (ANRS CO13 HEPAVIH Cohort). AIDS Behav 2020; 24:1069-1084. [PMID: 31286317 DOI: 10.1007/s10461-019-02585-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Mortality among individuals co-infected with HIV and hepatitis C virus (HCV) is relatively high. We evaluated the association between psychoactive substance use and both HCV and non-HCV mortality in HIV/HCV co-infected patients in France, using Fine and Gray's competing-risk model adjusted for socio-demographic, clinical predictors and confounding factors, while accounting for competing causes of death. Over a 5-year median follow-up period, 77 deaths occurred among 1028 patients. Regular/daily cannabis use, elevated coffee intake, and not currently smoking were independently associated with reduced HCV-mortality (adjusted sub-hazard ratio [95% CI] 0.28 [0.10-0.83], 0.38 [0.15-0.95], and 0.28 [0.10-0.79], respectively). Obesity and severe thinness were associated with increased HCV-mortality (2.44 [1.00-5.93] and 7.25 [2.22-23.6] versus normal weight, respectively). Regular binge drinking was associated with increased non-HCV-mortality (2.19 [1.10-4.37]). Further research is needed to understand the causal mechanisms involved. People living with HIV/HCV co-infection should be referred for tobacco, alcohol and weight control interventions and potential benefits of cannabis-based therapies investigated.
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Wang CC, Cheng PN, Kao JH. Systematic review: chronic viral hepatitis and metabolic derangement. Aliment Pharmacol Ther 2020; 51:216-230. [PMID: 31746482 DOI: 10.1111/apt.15575] [Citation(s) in RCA: 78] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Revised: 08/08/2019] [Accepted: 10/17/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND The liver has a critical role in the metabolism of glucose and lipids. Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection leads to a spectrum of liver disease including chronic hepatitis, cirrhosis and hepatocellular carcinoma. Metabolic syndrome (MetS) has a rising incidence owing to an epidemic of type 2 diabetes mellitus (T2DM) and obesity. Non-alcoholic fatty liver disease is a liver manifestation of MetS and has become the most common cause of chronic liver disease worldwide. AIM To summarise the interplay among hepatitis viruses, MetS and its components. METHODS We searched the literature about HBV, HCV infection, MetS, fatty liver and its components from PubMed. RESULTS With respect to the viral replication cycle, lipids are important mediators between viral entry and hepatocyte in HCV infection, but not in HBV infection. Thus, HCV infection is inversely associated with hyperlipidaemia and lipid rebound occurs following sustained viral response induced by interferon-based therapy or direct antiviral agents. In addition, HCV infection is positively associated with insulin resistance, hepatic steatosis, MetS and the risk of T2DM and atherosclerosis. In contrast, HBV infection may protect infected subjects from the development of MetS and hepatic steatosis. Accumulating evidence suggests that HBV infection is inversely associated with lipid metabolism, and exhibits no conclusive association with insulin resistance or the risk of T2DM and arteriosclerosis. CONCLUSIONS In patients with viral hepatitis and concurrent metabolic diseases, a multidisciplinary approach should be given rather than simply antiviral treatment.
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Affiliation(s)
- Chia-Chi Wang
- Department of Gastroenterology and Hepatology, Buddhist Tzu Chi Medical Foundation and School of Medicine, Taipei Tzu Chi Hospital, Tzu Chi University, Hualien, Taiwan
| | - Pin-Nan Cheng
- Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Internal Medicine, Department of Medical Research and Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
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14
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Wensveen FM, Šestan M, Turk Wensveen T, Polić B. 'Beauty and the beast' in infection: How immune-endocrine interactions regulate systemic metabolism in the context of infection. Eur J Immunol 2019; 49:982-995. [PMID: 31106860 DOI: 10.1002/eji.201847895] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Revised: 03/28/2019] [Accepted: 05/17/2019] [Indexed: 02/07/2023]
Abstract
The immune and endocrine systems ensure two vital functions in the body. The immune system protects us from lethal pathogens, whereas the endocrine system ensures proper metabolic function of peripheral organs by regulating systemic homeostasis. These two systems were long thought to operate independently. The immune system uses cytokines and immune receptors, whereas the endocrine system uses hormones to regulate metabolism. However, recent findings show that the immune and endocrine systems closely interact, especially regarding regulation of glucose metabolism. In response to pathogen encounter, cytokines modify responsiveness of peripheral organs to endocrine signals, resulting in altered levels of blood hormones such as insulin, which promotes the ability of the body to fight infection. Here we provide an overview of recent literature describing various mechanisms, which the immune system utilizes to modify endocrine regulation of systemic metabolism. Moreover, we will describe how these immune-endocrine interactions derail in the context of obesity. From a clinical perspective we will elaborate how infection and obesity aggravate the development of metabolic diseases such as diabetes mellitus type 2 in humans. In summary, this review provides a comprehensive overview of immune-induced changes in systemic metabolism following infection, with a focus on regulation of glucose metabolism.
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Affiliation(s)
- Felix M Wensveen
- Department of Histology and Embryology, University of Rijeka School of Medicine, Rijeka, Croatia
| | - Marko Šestan
- Department of Histology and Embryology, University of Rijeka School of Medicine, Rijeka, Croatia
| | - Tamara Turk Wensveen
- Department of Endocrinology, Diabetes and Metabolic Diseases, Clinical hospital center Rijeka, Rijeka, Croatia
| | - Bojan Polić
- Department of Histology and Embryology, University of Rijeka School of Medicine, Rijeka, Croatia
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15
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Ren H, Wang J, Gao Y, Yang F, Huang W. Metabolic syndrome and liver-related events: a systematic review and meta-analysis. BMC Endocr Disord 2019; 19:40. [PMID: 31023282 PMCID: PMC6485158 DOI: 10.1186/s12902-019-0366-3] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2019] [Accepted: 04/08/2019] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Previous studies have suggested that metabolic syndrome (MetS) and its component conditions are linked to the development of many benign or malignant diseases. Some studies have described relationships among metabolic syndrome or diabetes and liver cancer, but not many articles described the relationships between MetS and cirrhosis, acute hepatic failure, end-stage liver disease, and even death. However, liver cancers, cirrhosis, acute hepatic failure, end-stage liver disease, and liver-related mortality-collectively described as liver-related events (LREs)-may have different relationships with MetS. We undertook this meta-analysis to examine the association between MetS and LREs, and to determine whether geographic region or hepatitis B virus (HBV) positivity might influence the association. METHODS Relevant studies were identified from PubMed, EMBASE, and the Cochrane database. Two reviewers independently searched records from January 1980 to December 2017. The search terms included 'metabolic syndrome', 'diabetes mellitus', 'insulin resistance syndrome', and 'metabolic abnormalities', combined with 'cirrhosis', 'hepatic fibrosis ', 'hepatocellular carcinoma', 'complication', 'LRE', 'HCC', 'liver-related events', and 'liver cancer'. No language restriction was applied to the search. We chose the studies reporting an association between MetS and LREs. We used Begg's and Egger's tests and visually examined a funnel plot to assess publication bias. All analyses were conducted in Stata 14.0 software. RESULTS There were 19 studies (18 cohort and 1 case-control) included in the analysis, with a total of 1,561,457 participants. The subjects' ages ranged from 18 to 84 years. The combined analysis showed an overall 86% increase risk of LREs in cases with MetS (RR: 1.86,95% CI: 1.56-2.23). The funnel plot was asymmetrical, and the Egger's test p values showed a publication bias in this meta analysis. However, through the trim and fill method, we obtained a new RR value for LREs with MetS of 1.49 (95% CI: 1.40-1.58, p = 0.000). There was no obvious difference with the two answers, so we concluded that the results were robust. For hepatitis B positive patients, the RR for MetS and LREs was 2.15 (95% CI:1.02-4.53, p = 0.038), but for the hepatitis B negative patients, the RR was 1.85 (95% CI:1.53-2.24, p = 0.000). And for non-Asians, the RR for MetS and LREs was 2.21 (95% CI: 1.66-2.69, p = 0.000), while for Asians, the RR was 1.73 (95% CI: 1.35-2.22, p = 0.000). CONCLUSIONS This meta-analysis showed that MetS is associated with a moderately increased risk of LREs prevalence. Patients with MetS together with hepatitis B are more likely to develop hepatic events. For non-Asians, MetS is more likely to increase the incidence of LREs.
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Affiliation(s)
- Huina Ren
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016 China
| | - Junna Wang
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016 China
| | - Yue Gao
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016 China
| | - Fuwei Yang
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016 China
| | - Wenxiang Huang
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016 China
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16
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Yilmaz Y, Colak Y, Kurt R, Senates E, Eren F. Linking Nonalcoholic Fatty Liver Disease to Hepatocellular Carcinoma: From Bedside to Bench and Back. TUMORI JOURNAL 2018; 99:10-6. [DOI: 10.1177/030089161309900102] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Aims and background Nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) are two major causes of liver disease worldwide. Epidemiological and clinical data have clearly demonstrated that NAFLD and its associated metabolic abnormalities are a risk factor for HCC. Traditionally, the mechanisms whereby NAFLD acts as a risk for HCC are believed to include replicative senescence of steatotic hepatocytes and compensatory hyperplasia of progenitor cells as a reaction to chronic hepatic injury. Recent years have witnessed significant advances in our understanding of the mechanisms underlying the link between NAFLD and HCC. Methods In the present review, we provide an update on the pathophysiological pathways linking NAFLD and its associated metabolic derangements to malignant hepatic transformation, with a special focus on insulin resistance, adipokines, inflammation, and angiogenesis. We will also discuss the potential therapeutic implications that such molecular links carry. Results Although treating NAFLD could reduce the risk of malignant hepatic transformation, no long-term studies focusing on this issue have been conducted thus far. Insulin resistance, inflammation as well as derangements in adipokines and angiogenic factors associated with NAFLD are closely intertwined with the risk of developing HCC. Conclusions Traditional therapeutic approaches in NAFLD including metformin and statins may theoretically reduce the risk of HCC by acting on common pathophysiological pathways shared by NAFLD and HCC.
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Affiliation(s)
- Yusuf Yilmaz
- Institute of Gastroenterology, School
of Medicine, Marmara University, Istanbul
- Department of Gastroenterology, School
of Medicine, Marmara University, Istanbul
| | - Yasar Colak
- Department of Gastroenterology,
Faculty of Medicine, Istanbul Medeniyet University, Istanbul
| | - Ramazan Kurt
- Department of Gastroenterology, School
of Medicine, Marmara University, Istanbul
| | - Ebubekir Senates
- Department of Gastroenterology, School
of Medicine, Dicle University, Diyarbakir
| | - Fatih Eren
- Institute of Gastroenterology, School
of Medicine, Marmara University, Istanbul
- Department of Medical Biology and
Genetics, School of Medicine, Marmara University, Istanbul, Turkey
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Blumenthal MJ, Ujma S, Katz AA, Schäfer G. The Role of Type 2 Diabetes for the Development of Pathogen-Associated Cancers in the Face of the HIV/AIDS Epidemic. Front Microbiol 2017; 8:2368. [PMID: 29238337 PMCID: PMC5712558 DOI: 10.3389/fmicb.2017.02368] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2017] [Accepted: 11/16/2017] [Indexed: 12/16/2022] Open
Abstract
The contribution of HIV to the development of pathogen-associated cancers has long been recognized, as has the contribution of type 2 diabetes for the development of several types of cancer. While HIV/AIDS-associated immunosuppression reduces immunosurveillance and indirectly contributes favorably to cancerogenesis, diabetes directly increases cancer development due to chronic low-grade inflammation, dysregulated glucose metabolism, hyperactivation of insulin-responsive pathways, and anti-apoptotic signaling. Pathogen-associated cancers contribute significantly to the cancer burden particularly in low- and middle-income countries. In those countries, the incidence of type 2 diabetes has increased alarmingly over the last decades, in part due to rapid changes in diet, lifestyle, and urbanization. It is likely that the HIV/AIDS epidemic and the steadily increasing rate of type 2 diabetes display synergistic effects on oncogenesis. Although this possible link has not been extensively investigated, it might become more important in the years to come not least due to the stimulating effects of antiretroviral therapy on the development of type 2 diabetes. This review provides an overview of the current understanding of pathogen- and diabetes- associated cancers with focus on geographical regions additionally burdened by the HIV/AIDS epidemic. As both HIV and carcinogenic infections as well as the onset of type 2 diabetes involve environmental factors that can be avoided to a certain extent, this review will support the hypothesis that certain malignancies are potentially preventable. Deploying effective infection control strategies together with educational policies on diet and lifestyle may in the long term reduce the burden of preventable cancers which is of particular relevance in low-resource settings.
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Affiliation(s)
| | | | | | - Georgia Schäfer
- Receptor Biology Research Unit, Division of Medical Biochemistry and Structural Biology, Institute of Infectious Disease and Molecular Medicine, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, SA-MRC Gynecology Cancer Research Centre, University of Cape Town, Cape Town, South Africa
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18
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Insulin resistance is associated with esophageal varices in alcoholic liver disease patients. Eur J Gastroenterol Hepatol 2016; 28:792-6. [PMID: 26982337 DOI: 10.1097/meg.0000000000000627] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIM Insulin resistance plays an important role in chronic liver disease, where it has been associated with the progression of fibrosis and correlated with portal hypertension in cirrhotic patients with mixed etiology. However, the impact of insulin resistance in alcoholic liver disease remains mostly unknown. The aim of this study was to evaluate the association between insulin resistance, portal hypertension, severity of liver disease, and mortality in patients with alcoholic cirrhosis. PATIENTS AND METHODS A total of 106 consecutive alcoholic cirrhotic patients undergoing hepatic venous pressure gradient measurement at Erasme Hospital were included. Insulin resistance was estimated using the homeostatic model assessment-2 index. RESULTS The median model for end-stage liver disease (MELD) score was 15 (9-21) and the mean hepatic venous pressure gradient was16.3±6 mmHg. Twenty-six percent of the patients had compensated cirrhosis. Insulin resistance was significantly associated with portal hypertension in compensated cirrhotic patients and with the presence of esophageal varices, but was not associated with the MELD score and mortality. MELD score was the only independent covariate associated with mortality at 6 (P<0.001) and 12 months (P<0.001). CONCLUSION Insulin resistance is associated with the presence of esophageal varices, suggesting that the presence of insulin resistance could be harmful to alcoholic liver disease patients.
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19
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Gjærde LI, Shepherd L, Jablonowska E, Lazzarin A, Rougemont M, Darling K, Battegay M, Braun D, Martel-Laferriere V, Lundgren JD, Rockstroh JK, Gill J, Rauch A, Mocroft A, Klein MB, Peters L. Trends in Incidences and Risk Factors for Hepatocellular Carcinoma and Other Liver Events in HIV and Hepatitis C Virus-coinfected Individuals From 2001 to 2014: A Multicohort Study. Clin Infect Dis 2016; 63:821-829. [PMID: 27307505 DOI: 10.1093/cid/ciw380] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2016] [Accepted: 05/25/2016] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND While liver-related deaths in human immunodeficiency virus (HIV) and hepatitis C virus (HCV)-coinfected individuals have declined over the last decade, hepatocellular carcinoma (HCC) may have increased. We describe the epidemiology of HCC and other liver events in a multicohort collaboration of HIV/HCV-coinfected individuals. METHODS We studied HCV antibody-positive adults with HIV in the EuroSIDA study, the Southern Alberta Clinic Cohort, the Canadian Co-infection Cohort, and the Swiss HIV Cohort study from 2001 to 2014. We calculated the incidence of HCC and other liver events (defined as liver-related deaths or decompensations, excluding HCC) and used Poisson regression to estimate incidence rate ratios. RESULTS Our study comprised 7229 HIV/HCV-coinfected individuals (68% male, 90% white). During follow-up, 72 cases of HCC and 375 other liver events occurred, yielding incidence rates of 1.6 (95% confidence interval [CI], 1.3, 2.0) and 8.6 (95% CI, 7.8, 9.5) cases per 1000 person-years of follow-up, respectively. The rate of HCC increased 11% per calendar year (95% CI, 4%, 19%) and decreased 4% for other liver events (95% CI, 2%, 7%), but only the latter remained statistically significant after adjustment for potential confounders. Older age, cirrhosis, and low current CD4 cell count were associated with a higher incidence of both HCC and other liver events. CONCLUSIONS In HIV/HCV-coinfected individuals, the crude incidence of HCC increased from 2001 to 2014, while other liver events declined. Individuals with cirrhosis or low current CD4 cell count are at highest risk of developing HCC or other liver events.
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Affiliation(s)
- Lars I Gjærde
- Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
| | - Leah Shepherd
- Department of Infection and Population Health, University College London, United Kingdom
| | - Elzbieta Jablonowska
- Department of Infectious Diseases and Hepatology, Medical University of Lodz, Poland
| | - Adriano Lazzarin
- Department of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy
| | | | | | - Manuel Battegay
- Divisions of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel
| | - Dominique Braun
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Switzerland
| | - Valerie Martel-Laferriere
- Department of Microbiology and Infectious Diseases, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Canada
| | - Jens D Lundgren
- Centre for Health & Infectious Disease Research, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark
| | | | - John Gill
- Department of Medicine, University of Calgary, Alberta, Canada
| | - Andri Rauch
- Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Switzerland
| | - Amanda Mocroft
- Department of Infection and Population Health, University College London, United Kingdom
| | - Marina B Klein
- Department of Medicine, Chronic Viral Illness Service, McGill University Health Center, Montreal, Canada
| | - Lars Peters
- Centre for Health & Infectious Disease Research, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark
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20
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Conti CB, Cavalcoli F, Fraquelli M, Conte D, Massironi S. Ultrasound elastographic techniques in focal liver lesions. World J Gastroenterol 2016; 22:2647-2656. [PMID: 26973405 PMCID: PMC4777989 DOI: 10.3748/wjg.v22.i9.2647] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2015] [Revised: 12/23/2015] [Accepted: 01/11/2016] [Indexed: 02/06/2023] Open
Abstract
Elastographic techniques are new ultrasound-based imaging techniques developed to estimate tissue deformability/stiffness. Several ultrasound elastographic approaches have been developed, such as static elastography, transient elastography and acoustic radiation force imaging methods, which include point shear wave and shear wave imaging elastography. The application of these methods in clinical practice aims at estimating the mechanical tissues properties. One of the main settings for the application of these tools has been liver stiffness assessment in chronic liver disease, which has been studied mainly using transient elastography. Another field of application for these techniques is the assessment of focal lesions, detected by ultrasound in organs such as pancreas, prostate, breast, thyroid, lymph nodes. Considering the frequency and importance of the detection of focal liver lesions through routine ultrasound, some studies have also aimed to assess the role that elestography can play in studying the stiffness of different types of liver lesions, in order to predict their nature and thus offer valuable non-invasive methods for the diagnosis of liver masses.
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21
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Chettouh H, Lequoy M, Fartoux L, Vigouroux C, Desbois-Mouthon C. Hyperinsulinaemia and insulin signalling in the pathogenesis and the clinical course of hepatocellular carcinoma. Liver Int 2015; 35:2203-17. [PMID: 26123841 DOI: 10.1111/liv.12903] [Citation(s) in RCA: 80] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2015] [Accepted: 06/09/2015] [Indexed: 12/11/2022]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer and is one of the leading causes of cancer-related death. The risk factors for HCC include cirrhosis, chronic viral hepatitis, heavy alcohol intake and metabolic diseases such as obesity, type 2 diabetes and metabolic syndrome. Insulin resistance is a common denominator of all of these conditions and is tethered to hyperinsulinaemia. Here, we give an overview of the recent advances linking hyperinsulinaemia to HCC development and progression. In particular, we summarise the underlying causes of hyperinsulinaemia in the setting of chronic liver diseases. We present epidemiological evidence linking metabolic diseases to HCC risk and HCC-related mortality, as well as the pathogenic cellular and molecular mechanisms explaining this relation. A better understanding of the mechanisms by which insulin participates in HCC biology might ultimately provide novel opportunities for prevention and treatment.
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Affiliation(s)
- Hamza Chettouh
- Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France.,INSERM, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France
| | - Marie Lequoy
- Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France.,INSERM, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France.,Service d'Hépatologie, AP-HP, Hôpital Saint-Antoine, Paris, France
| | - Laetitia Fartoux
- Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France.,INSERM, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France.,Service d'Hépatologie, AP-HP, Hôpital Saint-Antoine, Paris, France
| | - Corinne Vigouroux
- Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France.,INSERM, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France.,Laboratoire Commun de Biologie et Génétique Moléculaires AP-HP, Hôpital Saint-Antoine, Paris, France.,ICAN, Institute of Cardiometabolism and Nutrition, Paris, France
| | - Christèle Desbois-Mouthon
- Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France.,INSERM, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France
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22
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Regression of liver stiffness after sustained hepatitis C virus (HCV) virological responses among HIV/HCV-coinfected patients. AIDS 2015; 29:1821-30. [PMID: 26372388 DOI: 10.1097/qad.0000000000000787] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE We assessed the impact of a sustained virological response (SVR) on liver stiffness among HIV/hepatitis C virus (HCV)-coinfected patients enrolled in the ANRS CO13 HEPAVIH cohort. METHODS We studied HIV/HCV-coinfected patients who received at least one dose of any anti-HCV treatment and who had documented SVR status, a pretreatment FibroScan value of at least 7.1 kPa, and at least one posttreatment FibroScan value. The time required to achieve at least a 30% decrease in liver stiffness was analyzed by constructing Kaplan-Meier curves and using Cox proportional hazards models. RESULTS Among 98 patients treated for HCV infection with either pegylated interferon along with ribavirin (n = 89) or protease inhibitor-based triple therapy (n = 9), 53 patients (54%) had an SVR. Median follow-up was 44.6 (interquartile range: 28.8-58.9) months. The probability of achieving a 30% decrease in FibroScan values was 51% [95% confidence interval (CI): 39-66] in patients with an SVR and 21% in nonresponders (95% CI: 11-36) at 1 year, and 74% (61-86) and 28% (17-44) at 2 years, respectively. In the subgroup of 35 cirrhotic patients (pretreatment liver stiffness ≥12.5 kPa), 14 of 18 patients with an SVR and three of 17 nonresponders had a fibrosis score below 12.5 kPa at the last follow-up examination. Multivariable analysis showed that SVR was independently associated with a ≥30% reduction in liver stiffness, both in the overall study group (hazard ratio: 5.77; 95% CI: 2.00-16.62; P = 0.0012) and in cirrhotic patients (hazard ratio: 8.21; 95% CI: 2.15-31.34; P = 0.0021). Robustness analyses using FIB4 values showed similar results. CONCLUSION SVR is significantly associated with improvement in liver stiffness in HIV/HCV-coinfected patients, including those with cirrhosis.
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23
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Rosenthal E, Roussillon C, Salmon-Céron D, Georget A, Hénard S, Huleux T, Gueit I, Mortier E, Costagliola D, Morlat P, Chêne G, Cacoub P. Liver-related deaths in HIV-infected patients between 1995 and 2010 in France: the Mortavic 2010 study in collaboration with the Agence Nationale de Recherche sur le SIDA (ANRS) EN 20 Mortalité 2010 survey. HIV Med 2015; 16:230-239. [PMID: 25522874 DOI: 10.1111/hiv.12204] [Citation(s) in RCA: 63] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/04/2014] [Indexed: 12/20/2022]
Abstract
OBJECTIVES The aim of this study was to describe the proportion of liver-related diseases (LRDs) as a cause of death in HIV-infected patients in France and to compare the results with data from our five previous surveys. METHODS In 2010, 24 clinical wards prospectively recorded all deaths occurring in around 26 000 HIV-infected patients who were regularly followed up. Results were compared with those of previous cross-sectional surveys conducted since 1995 using the same design. RESULTS Among 230 reported deaths, 46 (20%) were related to AIDS and 30 (13%) to chronic liver diseases. Eighty per cent of patients who died from LRDs had chronic hepatitis C, 16.7% of them being coinfected with hepatitis B virus (HBV). Among patients who died from an LRD, excessive alcohol consumption was reported in 41%. At death, 80% of patients had undetectable HIV viral load and the median CD4 cell count was 349 cells/μL. The proportion of deaths and the mortality rate attributable to LRDs significantly increased between 1995 and 2005 from 1.5% to 16.7% and from 1.2‰ to 2.0‰, respectively, whereas they tended to decrease in 2010 to 13% and 1.1‰, respectively. Among liver-related causes of death, the proportion represented by hepatocellular carcinoma (HCC) dramatically increased from 5% in 1995 to 40% in 2010 (p = 0.019). CONCLUSIONS The proportion of LRDs among causes of death in HIV-infected patients seems recently to have reached a plateau after a rapid increase during the decade 1995-2005. LRDs remain a leading cause of death in this population, mainly as a result of hepatitis C virus (HCV) coinfection, HCC representing almost half of liver-related causes of death.
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Affiliation(s)
- E Rosenthal
- Service de Médecine Interne, Hôpital de l'Archet, CHU de Nice, Nice, France; Université de Nice-Sophia Antipolis, Nice, France
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Carrieri MP, Serfaty L, Vilotitch A, Winnock M, Poizot-Martin I, Loko MA, Lions C, Lascoux-Combe C, Roux P, Salmon-Ceron D, Spire B, Dabis F. Cannabis Use and Reduced Risk of Insulin Resistance in HIV-HCV Infected Patients: A Longitudinal Analysis (ANRS CO13 HEPAVIH). Clin Infect Dis 2015; 61:40-8. [PMID: 25778750 DOI: 10.1093/cid/civ217] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2014] [Accepted: 03/09/2015] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Diabetes and insulin resistance (IR) is common in human immunodeficiency virus-hepatitis C virus (HIV-HCV)-coinfected patients, a population also concerned with elevated cannabis use. Cannabis has been associated with reduced IR risk in some population-based surveys. We determined whether cannabis use was consistently associated with reduced IR risk in HEPAVIH, a French nationwide cohort of HIV-HCV-coinfected patients. METHODS HEPAVIH medical and sociobehavioral data were collected (using annual self-administered questionnaires). We used 60 months of follow-up data for patients with at least 1 medical visit where IR (using homeostatic model assessment of insulin resistance [HOMA-IR]) and cannabis use were assessed. A mixed logistic regression model was used to evaluate the association between IR risk (HOMA-IR > 2.77) and cannabis use (occasional, regular, daily). RESULTS Among the 703 patients included in the study (1287 visits), 323 (46%) had HOMA-IR > 2.77 for at least 1 follow-up visit and 319 (45%) reported cannabis use in the 6 months before the first available visit. Cannabis users (irrespective of frequency) were less likely to have HOMA-IR > 2.77 (odds ratio [95% confidence interval], 0.4 [.2-.5]) after adjustment for known correlates/confounders. Two sensitivity analyses with HOMA-IR values as a continuous variable and a cutoff value of 3.8 confirmed the association between reduced IR risk and cannabis use. CONCLUSIONS Cannabis use is associated with a lower IR risk in HIV-HCV-coinfected patients. The benefits of cannabis-based pharmacotherapies for patients concerned with increased risk of IR and diabetes need to be evaluated in clinical research and practice.
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Affiliation(s)
- Maria Patrizia Carrieri
- Institut national de la santé et de la recherche médicale (INSERM), Unité mixte de recherche (UMR)912 (Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale [SESSTIM]) Aix Marseille Université, UMR_S912, Institut de recherche pour le développement Observatoire Régional de la Santé Provence-Alpes-Côte-d'Azur, Marseille
| | - Lawrence Serfaty
- Service d'hépatologie, Hôpital Saint-Antoine, Assistance publique - Hôpitaux de Paris (APHP), INSERM UMR_938, Université Pierre&Marie-Curie, Paris
| | - Antoine Vilotitch
- Institut national de la santé et de la recherche médicale (INSERM), Unité mixte de recherche (UMR)912 (Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale [SESSTIM]) Aix Marseille Université, UMR_S912, Institut de recherche pour le développement Observatoire Régional de la Santé Provence-Alpes-Côte-d'Azur, Marseille
| | - Maria Winnock
- INSERM, U897 and Institut de santé publique d'épidémiologie et de développement, Université Victor Segalen, Bordeaux
| | - Isabelle Poizot-Martin
- Aix-Marseille Université, Assistance Publique - Hôpitaux de Marseille Sainte-Marguerite, Service d'Immuno-hématologie Clinique, INSERM U912 (SESSTIM)
| | - Marc-Arthur Loko
- INSERM, U897 and Institut de santé publique d'épidémiologie et de développement, Université Victor Segalen, Bordeaux
| | - Caroline Lions
- Institut national de la santé et de la recherche médicale (INSERM), Unité mixte de recherche (UMR)912 (Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale [SESSTIM]) Aix Marseille Université, UMR_S912, Institut de recherche pour le développement Observatoire Régional de la Santé Provence-Alpes-Côte-d'Azur, Marseille
| | | | - Perrine Roux
- Institut national de la santé et de la recherche médicale (INSERM), Unité mixte de recherche (UMR)912 (Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale [SESSTIM]) Aix Marseille Université, UMR_S912, Institut de recherche pour le développement Observatoire Régional de la Santé Provence-Alpes-Côte-d'Azur, Marseille
| | - Dominique Salmon-Ceron
- Service des Maladies Infectieuses et Tropicales, Hôpital Cochin, APHP- Université Paris Descartes, France
| | - Bruno Spire
- Institut national de la santé et de la recherche médicale (INSERM), Unité mixte de recherche (UMR)912 (Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale [SESSTIM]) Aix Marseille Université, UMR_S912, Institut de recherche pour le développement Observatoire Régional de la Santé Provence-Alpes-Côte-d'Azur, Marseille
| | - Francois Dabis
- INSERM, U897 and Institut de santé publique d'épidémiologie et de développement, Université Victor Segalen, Bordeaux
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Lim T. Metabolic syndrome in chronic hepatitis C infection: does it still matter in the era of directly acting antiviral therapy? Hepat Med 2014; 6:113-8. [PMID: 25506251 PMCID: PMC4259863 DOI: 10.2147/hmer.s60083] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Metabolic syndrome is prevalent in patients with hepatitis C virus (HCV) infection. Given the pandemic spread of HCV infection and metabolic syndrome, the burden of their interaction is a major public health issue. The presence of metabolic syndrome accelerates the progression of liver disease in patients with HCV infection. New drug development in HCV has seen an unprecedented rise in the last year, which resulted in better efficacy, better tolerance, and a shorter treatment duration. This review describes the underlying mechanisms and clinical effects of metabolic syndrome in HCV infection, as well as their importance in the era of new directly acting antiviral therapy.
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Affiliation(s)
- Tr Lim
- Centre for Liver Research and NIHR Biomedical Research Unit in Liver Disease, University of Birmingham and Liver and Hepatobiliary Unit, Queen Elizabeth Hospital Birmingham, UK
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Aleksandrova K, Boeing H, Nöthlings U, Jenab M, Fedirko V, Kaaks R, Lukanova A, Trichopoulou A, Trichopoulos D, Boffetta P, Trepo E, Westhpal S, Duarte-Salles T, Stepien M, Overvad K, Tjønneland A, Halkjær J, Boutron-Ruault MC, Dossus L, Racine A, Lagiou P, Bamia C, Benetou V, Agnoli C, Palli D, Panico S, Tumino R, Vineis P, Bueno-de-Mesquita B, Peeters PH, Gram IT, Lund E, Weiderpass E, Quirós JR, Agudo A, Sánchez MJ, Gavrila D, Barricarte A, Dorronsoro M, Ohlsson B, Lindkvist B, Johansson A, Sund M, Khaw KT, Wareham N, Travis RC, Riboli E, Pischon T. Inflammatory and metabolic biomarkers and risk of liver and biliary tract cancer. Hepatology 2014; 60:858-71. [PMID: 24443059 PMCID: PMC4231978 DOI: 10.1002/hep.27016] [Citation(s) in RCA: 158] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2013] [Revised: 01/09/2014] [Accepted: 01/15/2014] [Indexed: 12/20/2022]
Abstract
UNLABELLED Obesity and associated metabolic disorders have been implicated in liver carcinogenesis; however, there are little data on the role of obesity-related biomarkers on liver cancer risk. We studied prospectively the association of inflammatory and metabolic biomarkers with risks of hepatocellular carcinoma (HCC), intrahepatic bile duct (IBD), and gallbladder and biliary tract cancers outside of the liver (GBTC) in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Over an average of 7.7 years, 296 participants developed HCC (n=125), GBTC (n=137), or IBD (n=34). Using risk-set sampling, controls were selected in a 2:1 ratio and matched for recruitment center, age, sex, fasting status, and time of blood collection. Baseline serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), C-peptide, total high-molecular-weight (HMW) adiponectin, leptin, fetuin-a, and glutamatdehydrogenase (GLDH) were measured, and incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. After adjustment for lifestyle factors, diabetes, hepatitis infection, and adiposity measures, higher concentrations of CRP, IL-6, C-peptide, and non-HMW adiponectin were associated with higher risk of HCC (IRR per doubling of concentrations=1.22; 95% CI=1.02-1.46; P=0.03; 1.90; 95% CI=1.30-2.77; P=0.001; 2.25; 95% CI=1.43-3.54; P=0.0005; and 2.09; 95% CI=1.19-3.67; P=0.01, respectively). CRP was associated also with risk of GBTC (IRR=1.22; 95% CI=1.05-1.42; P=0.01). GLDH was associated with risks of HCC (IRR=1.62; 95% CI=1.25-2.11; P=0.0003) and IBD (IRR=10.5; 95% CI=2.20-50.90; P=0.003). The continuous net reclassification index was 0.63 for CRP, IL-6, C-peptide, and non-HMW adiponectin and 0.46 for GLDH, indicating good predictive ability of these biomarkers. CONCLUSION Elevated levels of biomarkers of inflammation and hyperinsulinemia are associated with a higher risk of HCC, independent of obesity and established liver cancer risk factors.
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Affiliation(s)
- Krasimira Aleksandrova
- Department of Epidemiology, German Institute of Human Nutrition Potsdam-RehbrückeNuthetal, Germany
| | - Heiner Boeing
- Department of Epidemiology, German Institute of Human Nutrition Potsdam-RehbrückeNuthetal, Germany
| | - Ute Nöthlings
- Institute of Epidemiology, Christian-Albrechts University of KielKiel, Germany
- Nutritional Epidemiology Unit, Department of Nutritional and Food Science, Institut für Ernährungs- und Lebensmittelwissenschaften, Rheinische Friedrich-Wilhelms-Universität BonnBonn, Germany
| | - Mazda Jenab
- International Agency for Research on Cancer (IARC/World Health Organization [WHO])Lyon, France
| | - Veronika Fedirko
- International Agency for Research on Cancer (IARC/World Health Organization [WHO])Lyon, France
- Department of Epidemiology, Rollins School of Public Health, Emory UniversityAtlanta, GA
- Winship Cancer Institute, Emory UniversityAtlanta, GA
| | - Rudolf Kaaks
- Division of Cancer Epidemiology, German Cancer Research CenterHeidelberg, Germany
| | - Annekatrin Lukanova
- Division of Cancer Epidemiology, German Cancer Research CenterHeidelberg, Germany
- Department of Medical Biosciences/Pathology, University of UmeåUmeå, Sweden
| | - Antonia Trichopoulou
- WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical SchoolAthens, Greece
- Hellenic Health FoundationAthens, Greece
| | - Dimitrios Trichopoulos
- Hellenic Health FoundationAthens, Greece
- Department of Epidemiology, Harvard School of Public HealthBoston, MA
- Bureau of Epidemiologic Research, Academy of AthensAthens, Greece
| | - Paolo Boffetta
- Institute for Translational Epidemiology, Mount Sinai School of MedicineNew York, NY
| | | | - Sabine Westhpal
- Institute of Clinical Chemistry, Otto-von-Guericke-University MagdeburgMagdeburg, Germany
| | - Talita Duarte-Salles
- International Agency for Research on Cancer (IARC/World Health Organization [WHO])Lyon, France
| | - Magdalena Stepien
- International Agency for Research on Cancer (IARC/World Health Organization [WHO])Lyon, France
| | - Kim Overvad
- Section for Epidemiology, Department of Public Health, Aarhus UniversityAarhus, Denmark
| | - Anne Tjønneland
- Diet, Genes and Environment, Danish Cancer Society Research CenterCopenhagen, Denmark
| | - Jytte Halkjær
- Diet, Genes and Environment, Danish Cancer Society Research CenterCopenhagen, Denmark
| | - Marie-Christine Boutron-Ruault
- Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health TeamVillejuif, France
- Université Paris SudUMRS 1018, Villejuif, France
- Institut Gustave RoussyVillejuif, France
| | - Laure Dossus
- Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health TeamVillejuif, France
- Université Paris SudUMRS 1018, Villejuif, France
- Institut Gustave RoussyVillejuif, France
| | - Antoine Racine
- Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health TeamVillejuif, France
- Université Paris SudUMRS 1018, Villejuif, France
- Institut Gustave RoussyVillejuif, France
| | - Pagona Lagiou
- WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical SchoolAthens, Greece
- Department of Epidemiology, Harvard School of Public HealthBoston, MA
- Bureau of Epidemiologic Research, Academy of AthensAthens, Greece
| | - Christina Bamia
- WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical SchoolAthens, Greece
- Hellenic Health FoundationAthens, Greece
| | - Vassiliki Benetou
- WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical SchoolAthens, Greece
- Hellenic Health FoundationAthens, Greece
| | - Claudia Agnoli
- Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale TumoriMilano, Italy
| | - Domenico Palli
- Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO)Florence, Italy
| | - Salvatore Panico
- Department of Clinical and Experimental Medicine, Federico II UniversityNaples, Italy
| | - Rosario Tumino
- Cancer Registry and Histopathology Unit, “M.P. Arezzo” HospitalRagusa, Italy
| | - Paolo Vineis
- HuGeF FoundationTurin, Italy
- Division of Epidemiology, Public Health and Primary Care, Imperial CollegeLondon, UK
| | - Bas Bueno-de-Mesquita
- National Institute for Public Health and the Environment (RIVM)Bilthoven, the Netherlands
- Department of Gastroenterology and Hepatology, University Medical CenterUtrecht, the Netherlands
| | - Petra H Peeters
- Division of Epidemiology, Public Health and Primary Care, Imperial CollegeLondon, UK
- Julius Center for Health Sciences and Primary Care, University Medical CenterUtrecht, the Netherlands
| | - Inger Torhild Gram
- Department of Community Medicine, Faculty of Health Sciences, University of TromsøTromsø, Norway
| | - Eiliv Lund
- Department of Community Medicine, Faculty of Health Sciences, University of TromsøTromsø, Norway
| | - Elisabete Weiderpass
- Department of Community Medicine, Faculty of Health Sciences, University of TromsøTromsø, Norway
- Department of Research, Cancer Registry of NorwayOslo, Norway
- Department of Medical Epidemiology and Biostatistics, Karolinska InstitutetStockholm, Sweden
- Samfundet FolkhälsanHelsinki, Finland
| | | | - Antonio Agudo
- Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of OncologyBarcelona, Spain
| | - María-José Sánchez
- Andalusian School of Public HealthGranada, Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP)Madrid, Spain
| | - Diana Gavrila
- Servicio de Epidemiología, Department of Epidemiology, Consejería de Sanidad y Politica SocialMurcia, Spain
- Navarre Public Health InstitutePamplona, Spain
| | - Aurelio Barricarte
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP)Madrid, Spain
- Navarre Public Health InstitutePamplona, Spain
| | - Miren Dorronsoro
- Public Health Direction, Basque Regional Health Department and BioDonostia Research Institute-CIBERESPSan Sebastian, Spain
| | - Bodil Ohlsson
- Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital, Lund UniversityMalmö, Sweden
| | - Björn Lindkvist
- Institute of Medicine, Sahlgrenska Academy, University of GothenburgGothenburg, Sweden
| | - Anders Johansson
- Department of Odontology/Public Health and Clinical Medicine, Umeå UniversityUmeå, Sweden
| | - Malin Sund
- Department of Surgical and Perioperative Sciences, Surgery and Public Health, Nutrition Research, Umea UniversityUmea, Sweden
| | - Kay-Tee Khaw
- Department of Public Health and Primary Care, University of CambridgeCambridge, UK
| | - Nicholas Wareham
- MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's HospitalCambridge, UK
| | - Ruth C Travis
- Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of OxfordOxford, UK
| | - Elio Riboli
- Division of Epidemiology, Public Health and Primary Care, Imperial CollegeLondon, UK
| | - Tobias Pischon
- Molecular Epidemiology Group, Max Delbrück Center for Molecular Medicine Berlin-BuchBerlin-Buch, Germany
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Avihingsanon A, Jitmitraparp S, Tangkijvanich P, Ramautarsing RA, Apornpong T, Jirajariyavej S, Putcharoen O, Treeprasertsuk S, Akkarathamrongsin S, Poovorawan Y, Matthews GV, Lange JMA, Ruxrungtham K. Advanced liver fibrosis by transient elastography, fibrosis 4, and alanine aminotransferase/platelet ratio index among Asian hepatitis C with and without human immunodeficiency virus infection: role of vitamin D levels. J Gastroenterol Hepatol 2014; 29:1706-1714. [PMID: 24730732 DOI: 10.1111/jgh.12613] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/14/2014] [Indexed: 12/23/2022]
Abstract
BACKGROUND AND AIM Vitamin D insufficiency plays an important role in liver fibrosis in hepatitis C virus (HCV)-infected patients. We assessed liver fibrosis by transient elastography and 25 hydroxy vitamin D [25(OH)D] status in HCV-infected patients, with (HIV/HCV) or without HIV co-infection (HCV) from Thailand. METHODS Fibrosis stage was defined as mild (< 7.1 kPa); moderate (7.2-9.4 kPa); severe (9.5-14 kPa), and cirrhosis (> 14 kPa). Hypovitaminosis D was defined as 25(OH)D < 30 ng/mL. Logistic regression analyses were used to assess predictors for significant fibrosis. Serum 25(OH) D levels, HCV genotypes (GT), interleukin-28B (IL28B) and HCV-RNA were assessed. RESULTS A total of 331 HCV and 130 HIV/HCV patients were enrolled (70% male, 35% people who inject drugs [PWIDs]). HCV GT distribution was as follows: GT3 47%, GT1 34%, GT6 17%. IL-28B CC genotype (rs12979860) were found in 88% of HIV/HCV and 85% of HCV. In HCV, liver fibrosis was mild in 56.5%; moderate in 18.4%; severe in 12.4%; and cirrhosis in 12.7%. In HIV/HCV, these figures were 30.6%, 27.8%, 17.6%, and 24.1%, respectively. Patients with significant fibrosis were more often male, older, with HIV infection, hypovitaminosis D, and less likely to be infected with GT6. Factors associated with significant fibrosis by multivariate analysis were HIV infection (adjusted odd ratio [95% confidential interval]: 2.67, 1.20-5.93), P = 0.016, Fib-4 score > 1.45 (6.30, 2.70-14.74), P < 0.001, and hypovitaminosis D (2.48, 1.09-5.67), P = 0.031. GT 6 was less likely to have advanced liver fibrosis (0.17, 0.05-0.65), P = 0.01. CONCLUSIONS HIV infection, Fib-4 score > 1.45, and hypovitaminosis D are strong and independent predictors for the presence of advanced fibrosis in our HCV-infected patients. These data highlight the urgent need of HCV treatment and vitamin D supplement in resource-limited settings.
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Affiliation(s)
- Anchalee Avihingsanon
- HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), The Thai Red Cross AIDS Research Center, Bangkok, Thailand; Division of Allergy and Immunology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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Scalera A, Tarantino G. Could metabolic syndrome lead to hepatocarcinoma via non-alcoholic fatty liver disease? World J Gastroenterol 2014; 20:9217-9228. [PMID: 25071314 PMCID: PMC4110551 DOI: 10.3748/wjg.v20.i28.9217] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2013] [Revised: 04/01/2014] [Accepted: 04/15/2014] [Indexed: 02/06/2023] Open
Abstract
It was estimated that from 2002 to 2008 the risk of developing cancer increased a quarter-fold in men and two-fold in women due to excessive BMI. Obesity, metabolic syndrome and type 2 diabetes mellitus are strictly related and are key pathogenetic factors of non-alcoholic fatty liver disease (NAFLD), the most frequent liver disease worldwide. The most important consequence of the "metabolic epidemics" is the probable rise in the incidence of hepatocarcinoma (HCC), and NAFLD is the major causative factor. Adipose tissue is not merely a storage organ where lipids are preserved as an energy source. It is an active organ with important endocrine, paracrine, and autocrine actions in addition to immune functions. Adipocytes produce a wide range of hormones, cytokines, and growth factors that can act locally in the adipose tissue microenvironment and systemically. In this article, the main roles of insulin growth factor (IGF)-1 and IGF-2 are discussed. The role of IGF-2 is not only confined to HCC, but it may also act in early hepato-carcinogenesis, as pre-neoplastic lesions express IGF-2 mRNA. IGF-1 and IGF-2 interact with specific receptors (IGF-1R and IGF-2R). IGF-1R is over-expressed in in vitro and in animal models of HCC and it was demonstrated that IGF ligands exerted their effects on HCC cells through IGF-1R and that it was involved in the degeneration of pre-neoplastic lesions via an increase in their mitotic activity. Both IGF-2R and TGF β, a growth inhibitor, levels are reduced in human HCC compared with adjacent normal liver tissues. Another key mechanism involves peroxisome proliferator-activated receptor (PPAR)γ. In in vitro studies, PPARγ inhibited various carcinomas including HCC, most probably by regulating apoptosis via the p21, p53 and p27 pathways. Finally, as a clinical consequence, to improve survival, efforts to achieve a "healthier diet" should be promoted by physicians and politicians.
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Wang YG, Wang P, Wang B, Fu ZJ, Zhao WJ, Yan SL. Diabetes mellitus and poorer prognosis in hepatocellular carcinoma: a systematic review and meta-analysis. PLoS One 2014; 9:e95485. [PMID: 24830459 PMCID: PMC4022589 DOI: 10.1371/journal.pone.0095485] [Citation(s) in RCA: 76] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2013] [Accepted: 03/27/2014] [Indexed: 12/12/2022] Open
Abstract
Background Previous studies suggested that diabetes mellitus was associated with cancer risk and prognosis, but studies investigating the relationship between diabetes mellitus and survival in patients with hepatocellular carcinoma (HCC) reported inconsistent findings. To derive a more precise estimate of the prognostic role of diabetes mellitus in HCC, we systematically reviewed published studies and carried out a meta-analysis. Methods Eligible articles were identified in electronic databases from their inception through September 16, 2013. To evaluate the correlation between diabetes mellitus and prognosis in HCC, the pooled hazard ratios (HR) and their 95% confidence intervals (95% CI) for poorer overall and disease-free survivals were calculated by standard meta-analysis techniques with fixed-effects or random-effects models. Results 21 studies with a total of 9,767 HCC patients stratifying overall survival and/or disease-free survival in HCC patients by diabetes mellitus status were eligible for meta-analysis. 20 studies with a total of 9,727 HCC cases investigated the overall survival, and 10 studies with a total of 2,412 HCC patients investigated the disease-free survival. The pooled HRs for overall survival and disease-free survival were 1.46 (95% CI, 1.29 to 1.66; P<0.001) and 1.57 (95% CI, 1.21 to 2.05; P = 0.001), respectively. The adjusted HRs for overall survival and disease-free survival were 1.55 (95% CI, 1.27 to 1.91; P<0.001) and 2.15 (95% CI, 1.75 to 2.63; P<0.001), respectively. In addition, for patients receiving hepatic resection, diabetes mellitus was associated with both poorer overall survival and poorer disease-free survival, and for patients receiving non-surgical treatment or patients receiving radiofrequency ablation, diabetes mellitus was associated with poorer overall survival. There was no evidence for publication bias. Conclusion Diabetes mellitus is independently associated with both poorer overall survival and poorer disease-free survival in HCC patients.
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Affiliation(s)
- Yan-Gang Wang
- Department of Endocrinology, the Affiliated Hospital of Medical College, Qingdao University, Qingdao, China
- * E-mail: (YGW); (BW)
| | - Peng Wang
- Department of Endocrinology, the Affiliated Hospital of Medical College, Qingdao University, Qingdao, China
| | - Bin Wang
- Department of Endocrinology, the Affiliated Hospital of Medical College, Qingdao University, Qingdao, China
- * E-mail: (YGW); (BW)
| | - Zheng-Ju Fu
- Department of Endocrinology, the Affiliated Hospital of Medical College, Qingdao University, Qingdao, China
| | - Wen-Juan Zhao
- Department of Endocrinology, the Affiliated Hospital of Medical College, Qingdao University, Qingdao, China
| | - Sheng-Li Yan
- Department of Endocrinology, the Affiliated Hospital of Medical College, Qingdao University, Qingdao, China
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Kang W, Tong HI, Sun Y, Lu Y. Hepatitis C virus infection in patients with HIV-1: epidemiology, natural history and management. Expert Rev Gastroenterol Hepatol 2014; 8:247-66. [PMID: 24450362 DOI: 10.1586/17474124.2014.876357] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Hepatitis C virus (HCV)-related liver diseases have contributed to increased morbidity and mortality in HIV-1-infected individuals in the era of effective antiretroviral therapy. HCV transmission patterns have changed among the HIV co-infected population during the last decade, with acute HCV infection emerging worldwide. HIV infection accelerates the progression of HCV-related liver diseases and consequently cirrhosis, liver failure, and hepatocellular carcinoma. However, the current standard treatment of HCV infection with pegylated interferon plus ribavirin results in only a limited viral response. Furthermore, cumbersome pill regimens, antiretroviral related hepatotoxicity, and drug interactions of HCV and HIV regimens complicate therapy strategies. Fortunately, in the near future, new direct-acting anti-HCV agents will widen therapeutic options for HCV/HIV co-infection. Liver transplantation is also gradually accepted as a therapeutic option for end stage liver disease of HCV/HIV co-infected patients.
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Affiliation(s)
- Wen Kang
- Department of Public Health Sciences, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA
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Bose SK, Ray R. Hepatitis C virus infection and insulin resistance. World J Diabetes 2014; 5:52-58. [PMID: 24567801 PMCID: PMC3932427 DOI: 10.4239/wjd.v5.i1.52] [Citation(s) in RCA: 79] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2013] [Revised: 12/20/2013] [Accepted: 01/14/2014] [Indexed: 02/05/2023] Open
Abstract
Approximately 170 million people worldwide are chronically infected with hepatitis C virus (HCV). Chronic HCV infection is the leading cause for the development of liver fibrosis, cirrhosis, hepatocellular carcinoma (HCC) and is the primary cause for liver transplantation in the western world. Insulin resistance is one of the pathological features in patients with HCV infection and often leads to development of type II diabetes. Insulin resistance plays an important role in the development of various complications associated with HCV infection. Recent evidence indicates that HCV associated insulin resistance may result in hepatic fibrosis, steatosis, HCC and resistance to anti-viral treatment. Thus, HCV associated insulin resistance is a therapeutic target at any stage of HCV infection. HCV modulates normal cellular gene expression and interferes with the insulin signaling pathway. Various mechanisms have been proposed in regard to HCV mediated insulin resistance, involving up regulation of inflammatory cytokines, like tumor necrosis factor-α, phosphorylation of insulin-receptor substrate-1, Akt, up-regulation of gluconeogenic genes like glucose 6 phosphatase, phosphoenolpyruvate carboxykinase 2, and accumulation of lipid droplets. In this review, we summarize the available information on how HCV infection interferes with insulin signaling pathways resulting in insulin resistance.
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Singh S, Fujii LL, Murad MH, Wang Z, Asrani SK, Ehman RL, Kamath PS, Talwalkar JA. Liver stiffness is associated with risk of decompensation, liver cancer, and death in patients with chronic liver diseases: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2013; 11:1573-84.e1-2; quiz e88-9. [PMID: 23954643 PMCID: PMC3900882 DOI: 10.1016/j.cgh.2013.07.034] [Citation(s) in RCA: 232] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2013] [Accepted: 07/25/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Liver stiffness measurement (LSM), using elastography, can independently predict outcomes of patients with chronic liver diseases (CLDs). However, there is much variation in reporting and consistency of findings. We performed a systematic review and meta-analysis to evaluate the association between LSM and outcomes of patients with CLDs. METHODS We performed a systematic review of the literature, through February 2013, for studies that followed up patients with CLDs prospectively for at least 6 months and reported the association between baseline LSM and subsequent development of decompensated cirrhosis or hepatocellular carcinoma (HCC), as well as mortality. Summary relative risk (RR) estimates per unit of LSM and 95% confidence intervals (CIs) were estimated using the random effects model. RESULTS Our final analysis included 17 studies, reporting on 7058 patients with CLDs. Baseline LSM was associated significantly with risk of hepatic decompensation (6 studies; RR, 1.07; 95% CI, 1.03-1.11), HCC (9 studies; RR, 1.11; 95% CI, 1.05-1.18), death (5 studies; RR, 1.22; 95% CI, 1.05-1.43), or a composite of these outcomes (7 studies; RR, 1.32; 95% CI, 1.16-1.51). We observed considerable heterogeneity among studies-primarily in the magnitude of effect, rather than the direction of effect. This heterogeneity could not be explained by variations in study locations, etiologies and stages of CLD, techniques to measure liver stiffness, adjustment for covariates, or method of imputing relationship in the meta-analysis. CONCLUSIONS Based on a meta-analysis of cohort studies, the degree of liver stiffness is associated with risk of decompensated cirrhosis, HCC, and death in patients with CLDs. LSM therefore might be used in risk stratification.
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Affiliation(s)
- Siddharth Singh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
| | - Larissa L. Fujii
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | | | - Zhen Wang
- Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, Minnesota
| | - Sumeet K. Asrani
- Division of Hepatology, Baylor University Medical Center, Dallas, Texas
| | - Richard L. Ehman
- Department of Diagnostic Radiology, Mayo Clinic, Rochester, Minnesota
| | - Patrick S. Kamath
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Jayant A. Talwalkar
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
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Serviddio G, Blonda M, Bellanti F, Villani R, Iuliano L, Vendemiale G. Oxysterols and redox signaling in the pathogenesis of non-alcoholic fatty liver disease. Free Radic Res 2013; 47:881-893. [PMID: 24000796 DOI: 10.3109/10715762.2013.835048] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Oxysterols are oxidized species of cholesterol coming from exogenous (e.g. dietary) and endogenous (in vivo) sources. They play critical roles in normal physiologic functions such as regulation of cellular cholesterol homeostasis. Most of biological effects are mediated by interaction with nuclear receptor LXRα, highly expressed in the liver as well as in many other tissues. Such interaction participates in the regulation of whole-body cholesterol metabolism, by acting as "lipid sensors". Moreover, it seems that oxysterols are also suspected to play key roles in several pathologies, including cardiovascular and inflammatory disease, cancer, and neurodegeneration. Growing evidence suggests that oxysterols may contribute to liver injury in non-alcoholic fatty liver disease. The present review focuses on the current status of knowledge on oxysterols' biological role, with an emphasis on LXR signaling and oxysterols' physiopathological relevance in NAFLD, suggesting new pharmacological development that needs to be addressed in the near future.
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Affiliation(s)
- G Serviddio
- C.U.R.E. Centre for Liver Diseases Research and Treatment, Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia , Italy
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Liver injury in HIV monoinfected patients: should we turn a blind eye to it? Clin Res Hepatol Gastroenterol 2012; 36:441-7. [PMID: 23079114 DOI: 10.1016/j.clinre.2012.06.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2012] [Revised: 06/03/2012] [Accepted: 06/06/2012] [Indexed: 02/04/2023]
Abstract
With the advent of combined antiretroviral therapies, liver diseases have emerged as a key issue in the management of HIV infection. In addition to hepatitis co-infection, a large spectrum of liver diseases can affect the prognosis of HIV infection. Acute or progressive hepatic injuries require an accurate diagnosis for a better clinical management. Here, we provide an overview of the main liver diseases associated with HIV infection, which are not covered by the widely documented field of viral hepatitis co-infection.
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