scholarly journals Mechanisms by Which Probiotic Bacteria Attenuate the Risk of Hepatocellular Carcinoma

2021 ◽  
Vol 22 (5) ◽  
pp. 2606
Author(s):  
Wasitha P.D. Wass Thilakarathna ◽  
H.P. Vasantha Rupasinghe ◽  
Neale D. Ridgway
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Primary Liver Cancer ◽  
Probiotic Bacteria ◽  
Chronic Infections ◽  
Alcoholic Fatty Liver ◽  
Antiviral Activities ◽  
Subsequent Activation ◽  
Extrinsic Risk

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the second leading cause of cancer-related deaths worldwide. Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV), alcoholic liver disease (ALD), and non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) are the major extrinsic risk factors of HCC development. Genetic background is pivotal in HCC pathogenesis, and both germline mutations and single nucleotide polymorphism (SNP) are intrinsic risk factors of HCC. These HCC risk factors predispose to hepatic injury and subsequent activation of fibrogenesis that progresses into cirrhosis and HCC. Probiotic bacteria can mitigate HCC risk by modulating host gut microbiota (GM) to promote growth of beneficial microbes and inhibit HCC-associated dysbiosis, thus preventing pathogen-associated molecular patterns (PAMPs)-mediated hepatic inflammation. Probiotics have antiviral activities against HBV and HCV infections, ameliorate obesity and risk of NAFLD/NASH, and their antioxidant, anti-proliferative, anti-angiogenic, and anti-metastatic effects can prevent the HCC pathogenesis. Probiotics also upregulate the expression of tumor suppressor genes and downregulate oncogene expression. Moreover, metabolites generated by probiotics through degradation of dietary phytochemicals may mitigate the risk of HCC development. These multiple anticancer mechanisms illustrate the potential of probiotics as an adjuvant strategy for HCC risk management and treatment.

scholarly journals Surveillance for Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease: Universal or Selective?

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1422 ◽  
Author(s):  
Maria Corina Plaz Torres ◽  
Giorgia Bodini ◽  
Manuele Furnari ◽  
Elisa Marabotto ◽  
Patrizia Zentilin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Fatty Liver ◽  
Primary Liver Cancer ◽  
Screening Tools ◽  
Virus Infections ◽  
Current Standard ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome

Hepatocellular carcinoma (HCC), the most frequent primary liver cancer, is the sixth most common cancer, the fourth leading cause of cancer-related deaths worldwide, and accounts globally for about 800,000 deaths/year. Early detection of HCC is of pivotal importance as it is associated with improved survival and the ability to apply curative treatments. Chronic liver diseases, and in particular cirrhosis, are the main risk factors for HCC, but the etiology of liver disease is rapidly changing due to improvements in the prevention and treatment of HBV (Hepatitis B virus) and HCV (Hepatitis C virus) infections and to the rising incidence of the metabolic syndrome, of which non-alcoholic fatty liver (NAFLD) is a manifestation. NAFLD is now a recognized and rapidly increasing cause of cirrhosis and HCC. Indeed, the most recent guidelines for NAFLD management recommend screening for HCC in patients with established cirrhosis. Screening in NAFLD patients without cirrhosis is not recommended; however, the prevalence of HCC in this group of NAFLD patients has been reported to be as high as 38%, a proportion significantly higher than the one observed in the general population and in non-cirrhotic subjects with other causes of liver disease. Unfortunately, solid data regarding the risk stratification of patients with non-cirrhotic NAFLD who might best benefit from HCC surveillance are scarce, and specific recommendations in this field are urgently needed due to the increasing NAFLD epidemic, at least in Western countries. To further complicate matters, liver ultrasonography, which represents the current standard for HCC surveillance, has a decreased diagnostic accuracy in patients with NAFLD, and therefore disease-specific surveillance tools will be required for the early identification of HCC in this population. In this review, we summarize the most recent evidence on the epidemiology and risk factors for HCC in patients with NAFLD, with and without cirrhosis, and the evidence supporting surveillance for early HCC detection in these patients, reviewing the potential limitations of currently recommended surveillance strategies, and assessing data on the accuracy of potential new screening tools. At this stage it is difficult to propose general recommendations, and best clinical judgement should be exercised, based on the profile of risk factors specific to each patient.

scholarly journals Determinants of Hepatocellular Carcinoma in the United States: Differences in Risk Factor and Genetic Susceptibility by Race/Ethnicity

2021 ◽  
pp. 18-33
Author(s):  
Mehwish Rafique ◽  
Dana Kristjansson
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Genetic Analysis ◽  
Genetic Susceptibility ◽  
The United States ◽  
Metabolic Risk Factors ◽  
Metabolic Risk ◽  
Alcoholic Fatty Liver ◽  
Race Ethnicity

Background: Hepatocellular carcinoma (HCC) is one of the few cancers with an increasing incidence and mortality worldwide. This study aims to determine the contribution of known risk factors for HCC by race and ethnicity. Methods: Data on race, ethnicity, age, and gender were obtained from National Health and Nutrition Examination Survey (NHANES). Population attributable fractions (PAFs) of risk factors were estimated using non-invasive scoring measures of Hepatitis B and C virus infection, excessive alcohol use, smoking, diabetes and emerging metabolic risk factors [non-alcoholic steatohepatitis advanced cirrhosis (NASH) and non-alcoholic fatty liver disease-advanced fibrosis (NAFLD-fib)] over a 10-year period, 1999-2002 and 2009-2012. Genetic analysis was performed using DisGenet platform by attaining the top enriched genes strongly related to HCC. Furthermore, cytoscape network was used to form a gene-disease network association. Results: NASH-cirrhosis increased in the overall population and among all race and ethnic groups. Both liver fat accumulation and ALT levels vary among different populations; however, Hispanics have the highest prevalence of NAFLD and elevated ALT levels. Non-Hispanic (NH) blacks and Hispanics had a 3 to 4 times higher PAF for HCC than whites attributed due to chronic liver diseases, including NASH-cirrhosis and NAFLD-fib. Our genetic analysis demonstrated that PNPLA3 polymorphism is strongly associated with NAFLD-fib, which appears to represent susceptibility to liver disease among the Hispanic community. Conclusion: Hispanics and NH blacks are at a disproportionately higher risk for HCC in part due to the higher prevalence of liver disease comorbidities, including NASH-cirrhosis and NAFLD-fib. Compared to NH whites, Hispanics and NH blacks have a higher baseline risk for liver cancer due to non-metabolic factors, which may include a genetic susceptibility. Metabolic risk factors have increased and are now contributing to nearly half of HCC cases in the US.

scholarly journals Etiology of Hepatocellular Carcinoma: Special Focus on Fatty Liver Disease

2020 ◽  
Vol 10 ◽  
Author(s):  
Diwakar Suresh ◽  
Akshatha N. Srinivas ◽  
Divya P. Kumar
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Chronic Liver ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Hepatocellular Carcinoma (HCC) is a highly aggressive cancer with mortality running parallel to its incidence and has limited therapeutic options. Chronic liver inflammation and injury contribute significantly to the development and progression of HCC. Several factors such as gender, age, ethnicity, and demographic regions increase the HCC incidence rates and the major risk factors are chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), carcinogens (food contaminants, tobacco smoking, and environmental toxins), and inherited diseases. In recent years evidence highlights the association of metabolic syndrome (diabetes and obesity), excessive alcohol consumption (alcoholic fatty liver disease), and high-calorie intake (nonalcoholic fatty liver disease) to be the prime causes for HCC in countries with a westernized sedentary lifestyle. HCC predominantly occurs in the setting of chronic liver disease and cirrhosis (80%), however, 20% of the cases have been known in patients with non-cirrhotic liver. It is widely believed that there exist possible interactions between different etiological agents leading to the involvement of diverse mechanisms in the pathogenesis of HCC. Understanding the molecular mechanisms of HCC development and progression is imperative in developing effective targeted therapies to combat this deadly disease. Noteworthy, a detailed understanding of the risk factors is also critical to improve the screening, early detection, prevention, and management of HCC. Thus, this review recapitulates the etiology of HCC focusing especially on the nonalcoholic fatty liver disease (NAFLD)- and alcoholic fatty liver disease (AFLD)-associated HCC.

scholarly journals Risk Factors of Hepatocellular Carcinoma in Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Wenpei Guo ◽  
Lixin Liu
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Systematic Review ◽  
Liver Disease ◽  
Cohort Studies ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Meta Analysis ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Abstract To better identify people at high risk of developing hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD), we aimed to conduct a systematic review and meta-analysis. Databases (including MEDLINE, EMBASE, Web of Science, the Cochrane Library, ClinicalTrials.gov) were searched up to March 2021. We included studies that reported odds ratios (ORs) or hazard ratios (HRs) and 95% confidence intervals. 24 studies (3 prospective cohort studies, 16 retrospective cohort studies, and 5 case-control studies) of 23 articles, with a total of 1004284 NAFLD cases and 3610 NAFLD-HCC cases, were finally included. The pooled data suggested male, older age, diabetes, low platelet count, and advanced liver fibrosis were important risk factors for HCC in NAFLD. Hypertension, overweight, low albumin, PNPLA3 genotype, dyslipidemia, abnormal liver enzymes were also risk factors worth concern. This study may contribute to the establishment of targeted screening and secondary prevention of HCC in patients with NAFLD.

scholarly journals Fructose Consumption and Hepatocellular Carcinoma Promotion

Livers ◽  
2021 ◽  
Vol 1 (4) ◽  
pp. 250-262
Author(s):  
Lisette Chávez-Rodríguez ◽  
Alejandro Escobedo-Calvario ◽  
Soraya Salas-Silva ◽  
Roxana U. Miranda-Labra ◽  
Leticia Bucio ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Primary Liver Cancer ◽  
Metabolic Reprogramming ◽  
Alcoholic Fatty Liver ◽  
Fructose Metabolism ◽  
High Fructose ◽  
Accumulation Of Lipids

Hepatocellular carcinoma (HCC) accounts for 85% of primary liver cancer, the third most common cause of cancer-related deaths worldwide. Its incidence has been increasing in both men and women. In Western countries, high-calorie diets, mainly rich in carbohydrates such as fructose, represent a significant concern due to their repercussions on the population’s health. A high-fructose diet is related to the development of Metabolic-Associated Fatty Liver Disease (MAFLD), formerly named Non-Alcoholic Fatty Liver Disease (NAFLD), and the progression of HCC as it potentiates the lipogenic pathway and the accumulation of lipids. However, fructose metabolism seems to be different between the stages of the disease, carrying out a metabolic reprogramming to favor the proliferation, inflammation, and metastatic properties of cancer cells in HCC. This review focuses on a better understanding of fructose metabolism in both scenarios: MAFLD and HCC.

Risk factors for non-alcoholic fatty liver disease are common in patients with non-B non-C hepatocellular carcinoma in India

2017 ◽  
Vol 36 (5) ◽  
pp. 373-379 ◽  
Author(s):  
Deepu David ◽  
Anantharam Raghavendran ◽  
Ashish Goel ◽  
C. Bharath Kumar ◽  
Thomas Alex Kodiatte ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

scholarly journals Hepatocellular carcinoma in nonalcoholic fatty liver disease with or without cirrhosis: a population-based study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kanokwan Pinyopornpanish ◽  
George Khoudari ◽  
Mohannad Abou Saleh ◽  
Chaisiri Angkurawaranon ◽  
Kanokporn Pinyopornpanish ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Fatty Liver ◽  
Alanine Aminotransferase ◽  
Fatty Liver Disease ◽  
Male Gender ◽  
Smoking History ◽  
Alcoholic Fatty Liver ◽  
Factors Associated

Abstract Background There are limited data regarding the factors associated with hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD) patients without cirrhosis. We sought to determine the prevalence and factors associated with HCC in NAFLD patients with or without cirrhosis. Methods Adults with NAFLD (June 2015 to May 2020) were identified using the electronic health record database (Explorys Inc, Cleveland, OH) from 26 major integrated US healthcare systems. The prevalence of HCC was calculated. Multivariable analyses adjusting for covariates were performed to evaluate the associated risk factors and the presence of HCC. Results A total of 392,800 NAFLD patients were identified. Among 1110 patients with HCC, 170 (15.3%) had no cirrhosis. The prevalence of HCC in non-cirrhotic and cirrhotic NAFLD patients was 4.6/10,000 persons (95% CI 3.9–5.3), and 374.4/10,000 persons (95% CI 350.9–398.8), respectively. Age > 65 years (adjusted OR; 3.37, 95% CI 2.47–4.59), ever had elevated alanine aminotransferase (2.69; 2.14–3.37), male gender (2.57; 1.88–3.49), smoker (1.75; 1.23–2.49), and diabetes (1.56; 1.15–2.11) were associated with HCC in non-cirrhotic NAFLD (all P < 0.05). The prevalence of HCC in the non-cirrhotic with all five risk factors was 45.5/10,000 persons (95% CI 17.4–73.6). The factors associated with HCC in cirrhotic NAFLD included clinical decompensation, age > 65 years, male gender, Hispanic race, elevated alanine aminotransferase, diabetes and smoker (all P < 0.05). Conclusions These data identified the major risk factors for the development of HCC in NAFLD patients. In the non-cirrhotics, older male patients with smoking history, diabetes and an elevated alanine aminotransferase had highest risk and may need increased judicious monitoring.

scholarly journals The Burden of Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease: Screening Issue and Future Perspectives

2019 ◽  
Vol 20 (22) ◽  
pp. 5613 ◽  
Author(s):  
Grazia Pennisi ◽  
Ciro Celsa ◽  
Antonina Giammanco ◽  
Federica Spatola ◽  
Salvatore Petta
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Screening Methods ◽  
Future Perspectives ◽  
Alcoholic Fatty Liver ◽  
Obesity And Diabetes ◽  
Alcoholic Fatty Liver Disease

In recent decades, non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease in the Western world, and the occurrence of its complications, such as hepatocellular carcinoma (HCC), has rapidly increased. Obesity and diabetes are considered not only the main triggers for the development of the disease, but also two independent risk factors for HCC. Single nucleotide polymorphisms (such as PNPLA3, TM6SF2 and MBOAT7) are related to the susceptibility to the development of HCC and its progression. Therefore, an appropriate follow-up of these patients is needed for the early diagnosis and treatment of HCC. To date, international guidelines recommend the use of ultrasonography with or without alpha-fetoprotein (AFP) in patients with advanced fibrosis. Furthermore, the use of non-invasive tools could represent a strategy to implement surveillance performance. In this review, we analyzed the main risk factors of NAFLD-related HCC, the validated screening methods and the future perspectives.

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