• Causal relationship
• Genome-wide association study
• Hepatocellular carcinoma
• Mendelian randomization
• Modifiable risk factors

• Chinese
• Chronic liver disease
• External validation
• Hepatocellular carcinoma
• Risk prediction
• Systematic review

• Humans
• China/epidemiology
• Risk Assessment/methods
• Adult
• Liver Neoplasms/epidemiology
• Chronic Disease
• Liver Diseases/epidemiology
• Carcinoma, Hepatocellular/epidemiology
• Carcinoma, Hepatocellular/diagnosis
• Incidence
• Middle Aged
• Male
• East Asian People

• cholangiocarcinoma
• hepatectomy
• liver enzyme
• nomogram
• prognostic factor

• National Natural Science Foundation of China
• Key Clinical Research Incubation Project of West China Hospital of Sichuan University

• Cohort study
• HCC
• HCC screening
• PRS
• Predictive model

• Humans
• Carcinoma, Hepatocellular/genetics
• Liver Neoplasms/genetics
• Genome-Wide Association Study
• Male
• Female
• Middle Aged
• Risk Assessment/methods
• Aged
• Genetic Predisposition to Disease
• Multifactorial Inheritance
• Risk Factors
• Adult
• Predictive Value of Tests
• Cohort Studies
• Polymorphism, Single Nucleotide
• Genetic Risk Score

• 82204122 National Natural Science Foundation of China
• BK20190652 Natural Science Foundation of Jiangsu Province
• BK20220320 Natural Science Foundation of Jiangsu Province
• 2022ZB416 Jiangsu Funding Program for Excellent Postdoctoral Talent
• 2021-50 Science and Technology Young Scientific and Technological Talents Project of Jiangsu Province
• 2021M701757 China Postdoctoral Science Foundation
• 22KJB330002 Natural Science Foundation of Jiangsu Higher Education Institutions
• 2019RU038 Chinese Academy of Medical Sciences

• Epidemiology
• Medical oncology

• Healthy Zhejiang One Million People Cohort
• Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province
• Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang
• Key Research and Development Program of Zhejiang Province

• Hepatocellular carcinoma
• Mendelian randomization
• Modifiable risk factors
• Trans-ancestry

• Female
• Humans
• Male
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/epidemiology
• Case-Control Studies
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Japan/epidemiology
• Liver Neoplasms/genetics
• Liver Neoplasms/epidemiology
• Mendelian Randomization Analysis
• Polymorphism, Single Nucleotide
• Risk Factors
• White People/genetics
• East Asian People/genetics

• diabetes
• liver cancer
• random forest
• risk prediction
• survival data

• S2019.A4.015.19S Government of Hong Kong

• apoptosis
• cancer
• cell death
• ferroptosis
• liver disease
• liver surgery
• pyroptosis

• R01 DK113592 NIDDK NIH HHS
• 1402/1 Deutsche Forschungsgemeinschaft

• Jinchang Cohort
• alkaline phosphatase-to-platelet ratio index
• fibrosis index based on four factors
• gamma-glutamyl-transpeptidase to platelet ratio
• hepatocellular carcinoma

• Humans
• Carcinoma, Hepatocellular
• Liver Neoplasms
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/pathology
• Alkaline Phosphatase
• Peptidyl Transferases
• Prospective Studies
• Platelet Count
• gamma-Glutamyltransferase
• ROC Curve
• Retrospective Studies
• Early Diagnosis

• 81673248 National Natural Science Foundation of China
• 2018ZX10732202 National Major Project on Infectious Diseases

• artificial intelligence
• big data
• cancer
• data fusion
• platform
• precision medicine

• Humans
• Artificial Intelligence
• Big Data
• Neoplasms/genetics
• Neoplasms/therapy
• Forecasting

• liver cancer
• cancer models
• cancer prevention

• Animals
• Rats
• Aspirin/therapeutic use
• B7-H1 Antigen
• Carcinoma, Hepatocellular/chemically induced
• Carcinoma, Hepatocellular/drug therapy
• Diethylnitrosamine/toxicity
• Inflammation/drug therapy
• Liver Neoplasms/chemically induced
• Liver Neoplasms/drug therapy

• 2021SF-227 Key Research and Development Program of Shaanxi
• 2022JCYB-770 Natural Science Foundation of Shaanxi Province

• camrelizumab
• hepatic arterial infusion chemotherapy
• lenvatinib
• neutrophil-to-lymphocyte ratio
• unresectable hepatocellular carcinoma

• funding

• ATF4
• ER stress
• Ferroptosis
• HCC
• NRF2
• SLC7A11
• Steatohepatitis

• Humans
• Mice
• Animals
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/pathology
• Non-alcoholic Fatty Liver Disease/complications
• Liver Neoplasms/genetics
• Liver Neoplasms/complications
• Ferroptosis
• Activating Transcription Factor 4/metabolism
• Cystine/metabolism
• Inflammation/complications
• Carcinogenesis
• Glutamates
• Amino Acid Transport System y+/genetics
• Amino Acid Transport System y+/metabolism

• R37 AI043477 NIAID NIH HHS
• P01 DK098108 NIDDK NIH HHS
• P42 ES010337 NIEHS NIH HHS
• R01 CA211794 NCI NIH HHS
• R01 DK103185 NIDDK NIH HHS
• R01 CA118165 NCI NIH HHS
• R01 DK113171 NIDDK NIH HHS
• R01 CA234128 NCI NIH HHS
• R01 CA198103 NCI NIH HHS
• R01 DK120714 NIDDK NIH HHS
• P01 CA128814 NCI NIH HHS

• hepatobiliary cancer
• nested case-control study
• pancreatic cancer
• prospective cohort
• risk stratification

• Humans
• Aged
• Carcinoma, Hepatocellular/epidemiology
• Liver Neoplasms/epidemiology
• Prospective Studies
• East Asian People
• Risk Factors
• Biliary Tract Neoplasms/epidemiology
• Biliary Tract Neoplasms/pathology
• Pancreatic Neoplasms/epidemiology

• 2019YFC1315905 National Key Research and Development Program of China
• 82021005 Natural Science Foundation of China
• WJ2021M102 Health Commission of Hubei Province Scientific Research Project
• 2019kfyXJJS036 Fundamental Research Funds for the Central Universities

• Epidemiology
• Hepatocellular carcinoma
• Non-alcoholic fatty liver disease
• Risk factor
• Treatment strategy

• Ghr knockout mouse
• diethylnitrosamine
• growth hormone receptor
• hepatocellular carcinoma

• R01 CA151533 NCI NIH HHS
• R01 CA244845 NCI NIH HHS
• R01 CA260872 NCI NIH HHS
• National Institutes of Health/National Cancer Institute
• Anderson Cancer Center

It is generally accepted that the incidence of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-associated patients is higher than that in hepatitis B virus (HBV)-associated patients. The reason why this difference in the incidence of HCC occurs in patients with HBV and HCV infections remains unclear. We report the possibility that the contributing power of inflammation, which is the main risk factor for developing HCC, may be different with HBV and HCV infections.

To investigate this, we surveyed the hazard ratio of inflammation for HCC development which was identified by serum alanine aminotransferase (ALT) levels between patients with HBV and HCV infections.

The PubMed database was searched (2001-2021) for studies published in English regarding the incidence of HCC identifying 8924 HBV-and 7376 HCV- infected patients. From these studies, interferon-treated patients with both HBV and HCV infections were excluded. Furthermore, in HBV patients, those administered nucleos(t)ide analogues were excluded, and in HCV patients, those administered direct acting antivirals were also excluded. Studies citing hazard ratios of HCC regarding inflammation (serum elevated alanine aminotransferase levels) were selected. Finally, there were 14 studies of HBV- infected patients and 8 studies of HCV-infected patients. We calculated the hazard ratio in patients in an inflammatory state (serum ALT levels were above the normal range).

In the 14 studies of HBV patients, the average hazard ratio (HR) of elevated ALT for developing HCC was 2.74 [1.98-3.77] and that in the 8 studies of HCV-infected patients was 5.51 [3.08-9.83]. The HR of inflammation for HCC development in HCV-associated liver diseases is about twice that in HBV-associated liver diseases. HR in HCV-infected patients was significantly (P = 0.0391) higher than that in HBV-infected patients. In hepatitis B patients, the abnormal range adopted was 28-45 IU/L, and in hepatitis C patients, it was 20-50 IU/L. It was demonstrated that the abnormal ALT levels adopted in hepatitis B and C patients were very similar in this series.

The difference in the incidence of HCC development between HBV and HCV patients may depend on the difference in the hazard risk of ALT between HBV and HCV infections.

• Hazard ratio of alanine aminotransferase
• Hepatitis B virus
• Hepatitis C virus
• Hepatocellular carcinoma
• Elevated alanine aminotransferase

• HCC screening
• hepatocellular carcinoma
• metabolic syndrome
• nonalcoholic fatty liver disease
• nonalcoholic steatohepatitis

In addition to HBV/HCV causing hepatocellular carcinoma (HCC), other risk factors including obesity and alcohol drinking also increase risk. We describe the cumulative risk of HCC and mortality from liver-related disease by selected modifiable risk factors among a non-hepatitis virus-infected population.

For a community-based cohort, residents aged 30–65 years living in 7 townships in Taiwan were recruited, and have been followed up since 1991. A total of 18,541 individuals were seronegative for markers of chronic infection of HBV/HCV and with no history of HCC at baseline. New non-HBV/HCV HCC cases and liver-related deaths were ascertained through data linkage to the National Cancer Registry and Death Certification System from 1 January 1991 through 31 December 2017.

There were 207 HCC cases and 215 liver-related deaths identified. The incidence rate of non-HBV/HCV HCC was 47.2 per 100,000 person-years. The mortality rate of liver-related death was 49.0 per 100,000 person-years. Baseline information on alcohol consumption, heart disease, diabetes, elevated aspartate aminotransferase, and alanine aminotransferase predicted higher risks of HCC, with hazard ratios (HRs) (95% CIs) of 1.7 (1.1–2.5), 2.2 (1.1–4.1), 1.9 (1.0–3.5), 1.7 (1.1–2.4), and 1.6 (1.0–2.4), respectively. The HRs (95% CIs) of liver-related death were 2.3 (1.6–3.2) for alcohol consumption, 1.4 (1.1–1.9) for BMI ≥25 kg/m², 2.2 (1.4–3.3) for elevated aspartate aminotransferase, and 1.5 (1.0–2.4) for elevated alanine aminotransferase. The HR (95% CI) was 8.1 (3.6–18.5) for those with diabetes and elevated aspartate aminotransferase.

Individuals with elevated liver enzymes are at high risk of liver disease. Prevention and treatment of diabetes and heart disease are critical for non-hepatitis B, non-hepatitis C (NonB/C)-HCC.

We followed up individuals with no chronic HBV or HCV infection and described the risk of hepatocellular carcinoma (HCC, the most common form of primary liver cancer) and mortality from liver-related disease by modifiable risk factors. This study estimated the incidence rate of HCC by selected lifestyle risk factors and chronic diseases conditions. Alcohol consumption, heart disease, diabetes, and abnormal blood liver function tests showed a strong association with HCC risk and mortality.

•

Alcohol drinking increases risks of NonB/C-HCC and liver-related death.

• death
• hepatocellular carcinoma
• liver transplantation
• national health insurance database
• risk prediction

Hepatocellular carcinoma (HCC) is one of the major malignant diseases worldwide, characterized by growing incidence and high mortality rates despite apparent improvements in surveillance programs, diagnostic and treatment procedures, molecular therapies, and numerous research initiatives. Most HCCs occur in patients with liver cirrhosis, and the competing mortality risks from the tumor and the cirrhosis should be considered. Presently, previously identified risk factors, such as hepatitis virus infection, hepatic inflammation and fibrosis, and metabolic syndrome, may be used as chemoprevention targets. The application of precision medicine for HCC management challenges the one-size-fits-all concept; moreover, patients should no longer be treated entirely according to the histology of their tumor but based on molecular targets specific to their tumor biology. Next-generation sequencing emphasizes HCC molecular heterogeneity and aids our comprehension of possible vulnerabilities that can be exploited. Moreover, genetic sequencing as part of a precision medicine concept may work as a promising tool for postoperative cancer monitoring. The use of genetic and epigenetic markers to identify therapeutic vulnerability could change the diagnosis and treatment of HCC, which so far was based on Barcelona clinic liver cancer (BCLC) staging. In daily clinical practice, the shift from a stage-oriented to a therapeutic-oriented approach is needed to direct the choice of HCC treatment toward the potentially most effective option on an individual basis. The important factor in precision medicine is the promotion of patient management based on the individual approach, knowing that the final decision must be approved by a multidisciplinary expert team.

Patients with hepatitis B virus (HBV) were invited to receive ultrasound and alpha-protein examination directly in China. However, not all HBV carriers need to be subjected to further tests. This study aimed to develop a feasible primary screening method to narrow down potential high-risk individuals of liver cancer among populations with HBV.

Based on a prospective community-based cohort, potential risk factors were selected as the predictors, including age, sex, smoking, alcohol consumption, diabetes, liver cancer family history, liver diseases in mothers, source of water, body mass index (BMI), and psychological trauma. Cox proportional regression model was applied to predict the 3-year absolute risk of liver cancer and derive risk scores. The area under receiver operating characteristic curve (AUROC) and calibration plot were used to assess the performance of the model. Bootstrap resampling was used for internal validation.

Age, sex, BMI, alcohol consumption, liver diseases in mothers, and psychological trauma were independent risks of liver cancer. The 1- to 3-year AUROC of the prediction model was 71.15% (95% CI, 66.88–75.42), 71.16% (95% CI, 67.42–74.90), and 72.95% (95% CI, 64.20–81.70), respectively. The predicted risk was calibrated well with the observed liver cancer risk. Bootstrap resampling showed that C-index was 0.70 (0.67–0.74). A 32-point risk score was also developed and a score over 5 was identified for patients at extremely high risk.

A user-friendly primary screening method was created that could estimate the 3-year absolute risk of liver cancer and identify extremely high-risk individuals among the population with HBV.

• epidemiological risk factors
• high-risk population
• incidence risk
• prediction model
• primary liver cancer screening

• liver cancer
• nomogram
• risk management
• risk prediction
• screening

The increasing public health burden of Hepatocellular carcinoma (HCC) emphasizes the importance of defining important modifiable risk factors. In the following review, we will discuss the evidence for the relation of major lifestyle risk factors, mostly from large population-based studies. Generally, it is has been shown that healthy lifestyle habits, including minimizing obesity, eating a healthy diet, avoidance of smoking and alcohol, and increasing physical activity, have the potential to prevent HCC. Dietary composition is important beyond obesity. Consumption of n-3 polyunsaturated fatty acids, as well as fish and poultry, vegetables and fiber, are inversely associated with HCC, while red meat, saturated fat, cholesterol and sugar are related to increased risk. Data from multiple studies clearly show a beneficial effect for physical activity in reducing the risk of HCC. Smoking and alcohol can lead to liver fibrosis and liver cancer and jointly lead to an even greater risk.

The increasing burden of hepatocellular carcinoma (HCC) emphasizes the unmet need for primary prevention. Lifestyle measures appear to be important modifiable risk factors for HCC regardless of its etiology. Lifestyle patterns, as a whole and each component separately, are related to HCC risk. Dietary composition is important beyond obesity. Consumption of n-3 polyunsaturated fatty acids, as well as fish and poultry, are inversely associated with HCC, while red meat, saturated fat, and cholesterol are related to increased risk. Sugar consumption is associated with HCC risk, while fiber and vegetable intake is protective. Data from multiple studies clearly show a beneficial effect for physical activity in reducing the risk of HCC. However, the duration, mode and intensity of physical activity needed are yet to be determined. There is evidence that smoking can lead to liver fibrosis and liver cancer and has a synergistic effect with alcohol drinking. On the other hand, an excessive amount of alcohol by itself has been associated with increased risk of HCC directly (carcinogenic effect) or indirectly (liver fibrosis and cirrhosis progression. Large-scale intervention studies testing the effect of comprehensive lifestyle interventions on HCC prevention among diverse cohorts of liver disease patients are greatly warranted.

• alcohol
• dietary composition
• obesity
• physical activity
• smoking

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and affects patients of all genders, races, ethnicities, and socioeconomic status. While the causes of HCC are numerous, the primary etiology is cirrhosis from alcohol and non-alcoholic fatty liver disease in the United States and from infectious agents such as Hepatitis B and Hepatitis C in the developing world. In patients at-risk for developing HCC, screening is recommended with ultrasound imaging and alpha fetoprotein laboratory tests. In socioeconomically vulnerable patients, however, individual-level barriers (eg, insurance status) and contextual-level disparities (eg, health facilities) may not be readily available, thus limiting screening. Additional challenges faced by racial/ethnic minorities can further challenge the spectrum of HCC care and lead to inadequate screening, delayed diagnosis, and unequal access to treatment. Efforts to improve these multilevel factors that lead to screening and treatment disparities are critical to overcoming challenges. Providing health insurance to those without access, improving societal challenges that confine patients to a lower socioeconomic status, and reducing challenges to seeking healthcare can decrease the morbidity and mortality of these patients. Additionally, engaging with communities and allowing them to collaborate in their own healthcare can also help to attenuate these inequities. Through collaborative multidisciplinary change, we can make progress in tackling disparities in vulnerable populations to achieve health equity

• healthcare disparities
• hepatocellular carcinoma
• social determinants of health

Almost all Koreans are covered by mandatory national health insurance and are required to undergo health screening at least once every 2 years. We aimed to develop a machine learning model to predict the risk of developing hepatocellular carcinoma (HCC) based on the screening results and insurance claim data.

The National Health Insurance Service-National Health Screening database was used for this study (NHIS-2020-2-146). Our study cohort consisted of 417,346 health screening examinees between 2004 and 2007 without cancer history, which was split into training and test cohorts by the examination date, before or after 2005. Robust predictors were selected using Cox proportional hazard regression with 1000 different bootstrapped datasets. Random forest and extreme gradient boosting algorithms were used to develop a prediction model for the 9-year risk of HCC development after screening. After optimizing a prediction model via cross validation in the training cohort, the model was validated in the test cohort.

Of the total examinees, 0.5% (1799/331,694) and 0.4% (390/85,652) in the training cohort and the test cohort were diagnosed with HCC, respectively. Of the selected predictors, older age, male sex, obesity, abnormal liver function tests, the family history of chronic liver disease, and underlying chronic liver disease, chronic hepatitis virus or human immunodeficiency virus infection, and diabetes mellitus were associated with increased risk, whereas higher income, elevated total cholesterol, and underlying dyslipidemia or schizophrenic/delusional disorders were associated with decreased risk of HCC development (p < 0.001). In the test, our model showed good discrimination and calibration. The C-index, AUC, and Brier skill score were 0.857, 0.873, and 0.078, respectively.

Machine learning-based model could be used to predict the risk of HCC development based on the health screening examination results and claim data.

The online version contains supplementary material available at 10.1186/s12885-021-08498-w.

• Big data
• Liver neoplasms
• Machine learning
• Precision medicine

• cohort study
• liver cancer
• risk prediction model

• Adult
• Aged
• China/epidemiology
• Decision Support Techniques
• Female
• Hepatitis B/complications
• Hepatitis B/epidemiology
• Humans
• Incidence
• Liver Neoplasms/epidemiology
• Liver Neoplasms/virology
• Male
• Middle Aged
• Prospective Studies

• 29186 Cancer Research UK
• MC_UU_12026/2 Medical Research Council
• 202922 Wellcome Trust
• 212946 Wellcome Trust
• MC_UU_00017/1 Medical Research Council
• MC_U137686851 Medical Research Council
• Wellcome Trust
• 088158 Wellcome Trust
• 104085 Wellcome Trust

• joint effect
• low total cholesterol level
• normal-high alanine aminotransferase level
• primary liver cancer
• prospective study
• risk

• Adult
• Alanine Transaminase/blood
• China/epidemiology
• Cholesterol/blood
• Female
• Follow-Up Studies
• Humans
• Liver Neoplasms/blood
• Liver Neoplasms/epidemiology
• Male
• Middle Aged
• Prospective Studies
• Risk Assessment/methods
• Risk Assessment/statistics & numerical data
• Risk Factors
• Sex Factors

• Alanine aminotransferase
• diabetes
• hepatocellular carcinoma
• national cohort
• risk score

• Decision Learning Tree
• Hepatitis C virus
• Hepatocellular Carcinoma prediction
• Machine Learning Algorithm
• Serum marker

• Carcinoma, Hepatocellular/diagnosis
• Hepatitis C, Chronic/complications
• Humans
• Liver Neoplasms/diagnosis
• Machine Learning
• ROC Curve

• entecavir
• hepatocellular carcinoma
• risk
• tenofovir

• Hepatocellular carcinoma
• Intrahepatic cholangiocarcinoma
• Non-alcoholic fatty liver disease
• Non-alcoholic steatohepatitis
• Obesity

Exercise is predicted to have a positive effect among hepatocellular carcinoma (HCC) patients. However, these patients are hesitant to start and build up an exercise program for one major reason: the vague fear of developing hepatic decompensation, a potentially fatal condition that can lead to death. Integrating mobile health (mHealth) with individualized exercise programs could be a possible option for promoting physical capacity among HCC patients.

The aim of this study was to evaluate the efficacy and safety of rehabilitation exercises, which have been individually prescribed via an mHealth app, on physical fitness, body composition, biochemical profile, and quality of life among HCC patients.

A total of 37 HCC patients were enrolled in a 12-week course with an mHealth app program targeted to HCC patients. The wearable wristband device Neofit (Partron Co) was provided to participants, and recorded daily physical data, such as the number of steps, calorie expenditure, exercise time, and heart rate. Each participant was given an individualized rehabilitation exercise program that was prescribed and adjusted at the 6-week midintervention period based on the assessment results. At baseline, 6-week, and 12-week sessions, participants’ physical fitness levels (ie, 6-minute walk test, grip strength test, and 30-second chair stand test) were measured. Physical activity levels, as measured by the International Physical Activity Questionnaire-Short Form (IPAQ-SF); body composition (ie, body mass index, body fat percentage, and muscle mass); biochemical profiles; and quality of life, as measured by the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire C30, were assessed at baseline and at the end point. At the 6-week midpoint, exercise intensity was individually adjusted.

Of the 37 patients, 31 (84%) completed the 12-week intervention. Grip strength improved significantly after 12 weeks of the intervention. The 30-second chair stand test and the 6-minute walk test showed significant improvement from 0 to 6 weeks, from 0 to 12 weeks, and from 6 to 12 weeks. Muscle mass and the IPAQ-SF score increased significantly after 12 weeks of the intervention without biochemical deterioration.

Following 12 weeks of mHealth care, including an individually prescribed rehabilitation exercise program, we saw significant improvements in physical fitness, body composition, and physical activity without any complication or biochemical deterioration among compensated HCC patients who had completed therapy.

• exercise
• hepatocellular carcinoma
• mHealth
• physical activity
• physical fitness
• rehabilitation

• HCC
• HCC screening
• NAFLD

An accurate and simple risk prediction model that would facilitate earlier detection of pancreatic adenocarcinoma (PDAC) is not available at present. In this study, we compare different algorithms of risk prediction in order to select the best one for constructing a biomarker-based risk score, PancRISK.

Three hundred and seventy-nine patients with available measurements of three urine biomarkers, (LYVE1, REG1B and TFF1) using retrospectively collected samples, as well as creatinine and age, were randomly split into training and validation sets, following stratification into cases (PDAC) and controls (healthy patients). Several machine learning algorithms were used, and their performance characteristics were compared. The latter included AUC (area under ROC curve) and sensitivity at clinically relevant specificity.

None of the algorithms significantly outperformed all others. A logistic regression model, the easiest to interpret, was incorporated into a PancRISK score and subsequently evaluated on the whole data set. The PancRISK performance could be even further improved when CA19-9, commonly used PDAC biomarker, is added to the model.

PancRISK score enables easy interpretation of the biomarker panel data and is currently being tested to confirm that it can be used for stratification of patients at risk of developing pancreatic cancer completely non-invasively, using urine samples.

• LI-RADS
• Risk Score
• Surveillance
• hepatocellular carcinoma

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.

• HCC
• NAFLD
• PNPLA3
• TM6SF2
• hepatocellular carcinoma
• lncRNA
• long non-conding RNA
• miRNA
• micro RNA
• non-alcoholic fatty liver disease

• Animals
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/etiology
• Diabetes Complications/complications
• Humans
• Liver Neoplasms/diagnosis
• Liver Neoplasms/etiology
• Mass Screening/methods
• Non-alcoholic Fatty Liver Disease/complications
• Obesity/complications
• Risk Factors

• Activities of Daily Living
• Exercise Therapy
• Humans
• Liver Neoplasms/etiology
• Liver Neoplasms/pathology
• Liver Neoplasms/prevention & control
• Prospective Studies
• Risk Factors
• Sedentary Behavior

• Alcoholic liver disease (ALD)
• hepatocellular cancer (HCC)
• non-alcoholic fatty liver disease (NAFLD)