Metabolic disease as a risk of hepatocellular carcinoma.
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ABSTRACT:
SUBMITTER: Nishida N
PROVIDER: S-EPMC7820215 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
Publications
Metabolic disease as a risk of hepatocellular carcinoma.
Clinical and molecular hepatology 20201203 1
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Project description:Background & aimsThe metabolic dysfunction-associated fatty liver disease (MAFLD) is a new inclusive term proposed to replace non-alcoholic fatty liver disease (NAFLD). We analysed whether hepatocellular carcinoma (HCC) risk differs by MAFLD or NAFLD status in a large sample of asymptomatic adults.MethodsA cohort comprising 73,691 adults were followed up for the development of HCC. NAFLD was diagnosed among participants without other liver diseases (n = 65,992).ResultsParticipants with MAFLD showed higher incidence of HCC than those without MAFLD (0.37 and 0.24 per 1,000 person-years, respectively; p = 0.006). However, MAFLD was not an independent factor associated with HCC in multivariable adjusted analysis (hazard ratio [HR] 1.21; 95% CI 0.92-1.60). When stratified according to presence of other liver diseases, MAFLD was not associated with HCC in participants with other liver diseases. In participants without other liver diseases, both MAFLD (adjusted HR 1.84; 95% CI 1.09-3.11) and NAFLD (adjusted HR 1.71; 95% CI 1.01-2.90) were independent factors associated with HCC. When stratified according to NAFLD and MAFLD status, there was no HCC development among participants with NAFLD only during 8,936 person-years of follow-up, but this NAFLD-only group comprised 3.4%, and the majority of participants with hepatic steatosis fulfilled both NAFLD and MAFLD criteria.ConclusionsIn patients with other chronic liver diseases, the presence of MAFLD is not independently associated with an increased risk of HCC. For those without other chronic liver diseases, MAFLD largely overlaps with NAFLD and is associated with an increased risk of HCC.Impact and implicationsThis study investigated the usefulness of newly proposed nomenclature, metabolic dysfunction-associated fatty liver disease (MAFLD), over non-alcoholic fatty liver disease (NAFLD), in terms of predicting hepatocellular carcinoma. In patients with other chronic liver diseases, the presence of MAFLD is not independently associated with an increased risk of HCC. However, for those without chronic liver disease, MAFLD largely overlaps with NAFLD and is associated with an increased risk of HCC.
| S-EPMC10393797 | biostudies-literature
Project description:Non-alcoholic liver disease (NAFLD) defines liver abnormalities ranging from simple steatosis to nonalcoholic steatohepatitis with or without cirrhosis development, occurring in the absence of significant alcohol consumption, use of teratogenic medication, or hereditary disorders. The association between NAFLD and metabolic syndrome is well documented and widely recognized. Obesity, type 2 diabetes mellitus (T2DM), and dyslipidemia are the most common metabolic risk factors associated with NAFLD. Among the components of metabolic syndrome, current evidence strongly indicates obesity and diabetes as hepatocellular carcinoma (HCC) risk factors. There is also growing evidence that suggests an increased risk of HCC in NAFLD patients, even surpassing other etiologies in some high-income countries. Epidemiologic data demonstrate a parallel rise in prevalence of obesity, diabetes, NAFLD, and HCC. As obesity and its related diseases have steadily afflicted larger populations, HCC incidence is expected to increase in the future. Pathophysiologic mechanisms that underlie NAFLD development and subsequent progression to nonalcoholic steatohepatitis and cirrhosis (insulin resistance and hyperinsulinemia, oxidative stress, hepatic stellate cell activation, cytokine/adipocytokine signaling pathways, and genetic and environmental factors) appear to play a significant role in the development of NAFLD-related HCC. However, a comprehensive view of molecular mechanisms linking obesity, T2DM, and NAFLD-related HCC, as well as the exact sequence of molecular events, is still not understood in its entirety. Good-quality data are still necessary, and efforts should continue towards better understanding the underlying carcinogenic mechanisms of NAFLD-related HCC. In this paper, we aimed to centralize the most important links supporting these relationships, focusing on obesity, T2DM, and NAFLD-related HCC, as well as point out the major gaps in knowledge regarding the underlying molecular mechanisms behind them.
| S-EPMC4394070 | biostudies-literature
Project description:ImportanceIn the US, hepatocellular carcinoma (HCC) has been the most rapidly increasing cancer since 1980, and metabolic dysfunction-associated steatotic liver disease (MASLD) is expected to soon become the leading cause of HCC.ObjectiveTo develop a prediction model for HCC incidence in a cohort of patients with MASLD.Design, setting, and participantsThis prognostic study was conducted among patients aged at least 18 years with MASLD, identified using diagnosis of MASLD using International Classification of Diseases, Ninth Revision (ICD-9) or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis codes; natural language processing of radiology imaging report text, which identified patients who had imaging evidence of MASLD but had not been formally diagnosed; or the Dallas Steatosis Index, a risk equation that identifies individuals likely to have MASLD with good precision. Patients were enrolled from Kaiser Permanente Northern California, an integrated health delivery system with more than 4.6 million members, with study entry between January 2009 and December 2018, and follow-up until HCC development, death, or study termination on September 30, 2021. Statistical analysis was performed during February 2023 and January 2024.ExposureData were extracted from the electronic health record and included 18 routinely measured factors associated with MASLD.Main outcome and measuresThe cohort was split (70:30) into derivation and internal validation sets; extreme gradient boosting was used to model HCC incidence. HCC risk was divided into 3 categories, with the cumulative estimated probability of HCC 0.05% or less classified as low risk; 0.05% to 0.09%, medium risk; and 0.1% or greater, high risk.ResultsA total of 1 811 461 patients (median age [IQR] at baseline, 52 [41-63] years; 982 300 [54.2%] female) participated in the study. During a median (range) follow-up of 9.3 (5.8-12.4) years, 946 patients developed HCC, for an incidence rate of 0.065 per 1000 person-years. The model achieved an area under the curve of 0.899 (95% CI, 0.882-0.916) in the validation set. At the medium-risk threshold, the model had a sensitivity of 87.5%, specificity of 81.4%, and a number needed to screen of 406. At the high-risk threshold, the model had a sensitivity of 78.4%, a specificity of 90.1%, and a number needed to screen of 241.Conclusions and relevanceThis prognostic study of more than 1.8 million patients with MASLD used electronic health record data to develop a prediction model to discriminate between individuals with and without incident HCC with good precision. This model could serve as a starting point to identify patients with MASLD who may need intervention and/or HCC surveillance.
| S-EPMC11240192 | biostudies-literature
Project description:ObjectiveChronic hepatitis B (CHB) and metabolic dysfunction-associated steatotic liver disease (MASLD) are the leading causes of hepatocellular carcinoma (HCC). This study aimed to explore the impact of baseline MASLD on the risk of HCC development in patients with CHB receiving antiviral treatment.MethodsWe consecutively recruited 535 patients with CHB who initiated antiviral treatment between January 2007 and January 2023. The exclusion criteria included coexisting HDV, HCV, or HIV infection; other chronic liver diseases; extrahepatic malignancies; prior HCC; and HCC development within one year. A baseline liver biopsy was performed in 467 patients (87 %). MASLD was defined as hepatic steatosis diagnosed histologically or by imaging, combined with one cardiometabolic risk factor. The cumulative incidence of HCC and its associated factors was analyzed in patients with CHB, with and without MASLD.ResultsIn total, 535 treatment-naïve patients with CHB were included, with a median follow-up of 6.05 years. MASLD was not associated with an increased incidence of HCC in patients with CHB (HR: 1.17; 95 % CI: 0.77-1.79; p = 0.466). The cumulative incidence of HCC increased with the number of fulfilled cardiometabolic criteria (0-2 criteria vs. ≥ 3 criteria) (HR: 3.93; 95 % CI: 1.89-8.19; p < 0.001).Age (HR: 1.03, 95 % CI 1.01-1.06, p = 0.010), male sex (HR: 3.17; 95 % CI 1.34-7.53, p = 0.009), diabetes (HR: 2.81; 95 % CI 1.54-5.12, p < 0.001), and cirrhosis (HR:3.03; 95 % CI 1.57-5.5.86, p < 0.001) were independently associated with HCC development.ConclusionsIt was not MASLD, but rather the presence of multiple cardiometabolic risk factors in patients with CHB that was associated with the risk of HCC in those receiving antiviral treatment. Furthermore, older age, male sex, diabetes, and cirrhosis aggravated the risk of HCC in patients with CHB.
| S-EPMC11425165 | biostudies-literature
Project description:BackgroundThe obesity and hepatocellular carcinoma (HCC) risk association may differ by individuals' metabolic health status.AimTo investigate the association between obesity categories and HCC risk among individuals with different metabolic health phenotypes.MethodsA case-control study among 518 HCC cases and 1,036 frequency-matched controls was conducted. Body mass index (BMI) was assessed before diagnosis. Pre-diagnosis data on dyslipidemia, hypertension, and diabetes were used to categorize participants as metabolically healthy or metabolically unhealthy. Participants were further categorized into metabolically healthy normal weight (MHNW), metabolically healthy overweight (MHOW), metabolically healthy obese (MHO), metabolically unhealthy normal weight (MUNW), metabolically unhealthy overweight (MUOW), and metabolically unhealthy obese (MHO). We used logistic regression to calculate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs).ResultsBeing overweight (OR=1.68, 95%CI=1.21-2.34) or obese (OR=1.49, 95%CI=1.11-1.89) was associated with higher HCC risk. Among metabolically healthy participants, no association was found between being overweight or obese and HCC risk. However, among the metabolically unhealthy participants, being overweight (OR=1.89, 95%CI=1.31-2.72) or obese (OR=1.50, 95%CI=1.07-2.09) was associated with higher HCC risk. Compared to the MHNW phenotype, no association was found between the MHOW and MHO phenotypes and HCC risk, but the MUNW (OR=1.94, 95%CI=1.09-3.43), MUOW (OR=3.78, 95%CI=2.15-6.65), and MUO (OR=2.93, 95%CI=1.70-5.05) phenotypes were associated with higher HCC risk.ConclusionThe association between BMI and HCC appears to be restricted to individuals with underlying metabolic abnormalities.
| S-EPMC9213572 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD) is a fast-growing public health problem and predisposes to hepatocellular carcinoma (HCC) in a significant proportion of patients. Metabolic alterations might underlie the progression of NAFLD to HCC, but the magnitudes of risk and population-attributable risk fractions (PAFs) for various metabolic conditions that are associated with HCC risk in patients with NAFLD are unknown. We investigated the associations between metabolic conditions and HCC development in individuals with a prior history of NAFLD. The study included 11,245 participants in the SEER-Medicare database, comprising 1310 NAFLD-related HCC cases and 9835 NAFLD controls. We excluded individuals with competing liver diseases (e.g., alcoholic liver disease and chronic viral hepatitis). Baseline pre-existing diabetes mellitus, dyslipidemia, obesity, hypertension, hypothyroidism, and metabolic syndrome were assessed. Multivariable-adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). PAFs were also calculated for each metabolic condition. The results show that diabetes (OR = 2.39, 95% CI: 2.04-2.79), metabolic syndrome (OR = 1.73, 95% CI: 1.49-2.01), and obesity (OR = 1.62, 95% CI: 1.43-1.85) were associated with a higher HCC risk in individuals with NAFLD. The highest PAF for HCC was observed for pre-existing diabetes (42.1%, 95% CI: 35.7-48.5), followed by metabolic syndrome (28.8%, 95% CI: 21.7-35.9) and obesity (13.2%, 95% CI: 9.6-16.8). The major predisposing factors for HCC in individuals with NAFLD are diabetes mellitus, metabolic syndrome, and obesity, and their control would be critically important in mitigating the rising incidence of NAFLD-related HCC.
| S-EPMC9777437 | biostudies-literature
Project description:The rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and its more severe form, metabolic dysfunction-associated steatohepatitis (MASH), is closely linked with a heightened risk of hepatocellular carcinoma (HCC), the fourth leading cause of cancer-related deaths worldwide. Despite the elevated risk of HCC in patients with MASLD, the existing surveillance guidelines are inadequate, particularly for those without cirrhosis. This review evaluates current HCC surveillance practices in patients with MASLD and their shortcomings. It also highlights the critical need for enhanced HCC risk stratification and diagnostic accuracy through new techniques. In this review article, we performed a comprehensive literature review of studies focusing on HCC risk factors in MASLD/MASH patients from 2000 to 2023. We discussed that demographics, comorbidities, liver fibrosis, and genetic markers play critical roles in HCC risk stratification. Additionally, non-invasive tests (NITs) for fibrosis may improve the accuracy for HCC risk stratification and diagnosis. More recently, innovative approaches, such as machine learning techniques and liquid biopsy utilizing extracellular vesicles, cell-free DNA, and circulating tumor cells show promise in redefining early HCC detection. Thus, integrating these various risk factors could optimize early detection of HCC for the growing MASLD/MASH patient population. However, further research is needed to confirm their effectiveness and practical implementation in clinical settings.
| S-EPMC11535805 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are liver manifestations of the metabolic syndrome and can progress to hepatocellular carcinoma (HCC). Loss of Growth Hormone (GH) signaling is reported to predispose to NAFLD and NASH through direct actions on the liver. Here, we report that aged mice lacking hepatocyte Jak2 (JAK2L), an obligate transducer of Growth Hormone (GH) signaling, spontaneously develop the full spectrum of phenotypes found in patients with metabolic liver disease, beginning with insulin resistance and lipodystrophy and manifesting as NAFLD, NASH and even HCC, independent of dietary intervention. Remarkably, insulin resistance, metabolic liver disease, and carcinogenesis are prevented in JAK2L mice via concomitant deletion of adipocyte Jak2 (JAK2LA). Further, we demonstrate that GH increases hepatic lipid burden but does so indirectly via signaling through adipocyte JAK2. Collectively, these data establish adipocytes as the mediator of GH-induced metabolic liver disease and carcinogenesis. In addition, we report a new spontaneous model of NAFLD, NASH, and HCC that recapitulates the natural sequelae of human insulin resistance-associated disease progression. The work presented here suggests a attention be paid towards inhibition of adipocyte GH signaling as a therapeutic target of metabolic liver disease.
| S-EPMC6777921 | biostudies-literature
Project description:Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new nomenclature recently proposed by a panel of international experts so that the entity is defined based on positive criteria and linked to pathogenesis, replacing the traditional non-alcoholic fatty liver disease (NAFLD), a definition based on exclusion criteria. NAFLD/MAFLD is currently the most common form of chronic liver disease worldwide and is a growing risk factor for development of hepatocellular carcinoma (HCC). It is estimated than 25% of the global population have NAFLD and is projected to increase in the next years. Major Scientific Societies agree that surveillance for HCC should be indicated in patients with NAFLD/ MAFLD and cirrhosis but differ in non-cirrhotic patients (including those with advanced fibrosis). Several studies have shown that the annual incidence rate of HCC in NAFLD-cirrhosis is greater than 1%, thus surveillance for HCC is cost-effective. Risk factors that increase HCC incidence in these patients are male gender, older age, presence of diabetes and any degree of alcohol consumption. In non-cirrhotic patients, the incidence of HCC is much lower and variable, being a great challenge to stratify the risk of HCC in this group. Furthermore, large epidemiological studies based on the general population have shown that diabetes and obesity significantly increase risk of HCC. Some genetic variants may also play a role modifying the HCC occurrence among patients with NAFLD. The purpose of this review is to discuss the epidemiology, clinical and genetic risk factors that may influence the risk of HCC in NAFLD/MAFLD patients and propose screening strategy to translate into better patient care.
| S-EPMC8891669 | biostudies-literature
Project description:Although the metabolic syndrome is a commonplace topic, its potential threats to public health is a problem that cannot be neglected. As the living conditions improved significantly over the past few years, the morbidity of metabolic syndrome has also steadily risen, and the onset age is becoming younger. The hepatocellular carcinoma (HCC), is one of the most prevalent life-threatening human cancers worldwide, incidence of which is also on the rise, gradually occupied the top of the list associated with metabolic syndrome related complication. Despite the advanced improvement of HCC management, the lifestyle, environmental factors, obesity, hepatitis B virus (HBV) infection have been recognized as risk factors for the development of liver cancer. In recent years, genetic studies, especially the genome-wide association studies (GWASs) were widely performed, a new era of the human genome research was created, which has significantly promoted the study of complex disease genetics. These progresses have contributed to the discovery of abundant number of genomic loci convincingly linked with complex metabolic feature and HCC. In this review, we briefly summarize the association between metabolic syndrome and HCC, focusing on the genetic factors contributed to metabolic syndrome and HCC.
| S-EPMC5471064 | biostudies-literature