• Mexican Americans
• diabetes mellitus
• hepatocellular carcinoma
• interactions
• metformin

• P50 CA217674 NCI NIH HHS
• R01 CA186566 NCI NIH HHS

• alcohol
• hepatitis B
• hepatitis C
• hepatocellular carcinoma
• meta‐analysis

• Humans
• Carcinoma, Hepatocellular/epidemiology
• Carcinoma, Hepatocellular/etiology
• Liver Neoplasms/epidemiology
• Liver Neoplasms/etiology
• Hepatitis C/complications
• Hepatitis C/epidemiology
• Hepatitis B/complications
• Hepatitis B/epidemiology
• Alcohol Drinking/adverse effects
• Alcohol Drinking/epidemiology
• Coinfection/epidemiology
• Hepacivirus
• Hepatitis B virus
• Risk Factors
• Odds Ratio

• Cancer
• Metabolic
• Obesity
• Surgery
• Surveillance
• Treatment
• Viral hepatitis

• Humans
• Carcinoma, Hepatocellular/epidemiology
• Carcinoma, Hepatocellular/etiology
• Liver Neoplasms/epidemiology
• Liver Neoplasms/etiology
• Liver Diseases, Alcoholic/epidemiology
• Liver Diseases, Alcoholic/therapy
• Risk Factors
• Alcohol Drinking/adverse effects
• Alcohol Drinking/epidemiology
• Metabolic Syndrome/complications
• Metabolic Syndrome/epidemiology

• Body fat percentage
• Body mass index
• Hepatocellular carcinoma
• Immune cell infiltration
• Mendelian randomization
• Obesity

• Humans
• Carcinoma, Hepatocellular/genetics
• Liver Neoplasms/genetics
• Obesity/complications
• Obesity/genetics
• Genome-Wide Association Study
• Body Mass Index
• Risk Factors
• Insulin Resistance/genetics
• Tumor Microenvironment/genetics
• Mendelian Randomization Analysis

• alcoholism
• fatty live disease
• fibrosis
• inflammation
• oxidative stress

• Animals
• Rats, Wistar
• Diabetes Mellitus, Experimental
• Rats
• Diet, High-Fat/adverse effects
• Female
• Liver Cirrhosis/pathology
• Liver Cirrhosis/chemically induced
• Liver Cirrhosis/metabolism
• Diabetes Mellitus, Type 2/chemically induced
• Diabetes Mellitus, Type 2/metabolism
• Diabetes Mellitus, Type 2/pathology
• Liver/drug effects
• Liver/pathology
• Liver/metabolism
• Ethanol/toxicity
• Lipid Peroxidation/drug effects

• HBV
• HCV
• HIV
• South Africa
• illicit drug
• immune system

• Humans
• Substance-Related Disorders/complications
• South Africa/epidemiology
• Hepatitis C/virology
• Hepatitis C/transmission
• Hepatitis B/virology
• Hepatitis B/transmission
• HIV Infections/transmission
• HIV Infections/virology
• Virus Replication/drug effects
• Illicit Drugs/adverse effects
• Hepatitis B virus/physiology
• Virus Diseases/transmission
• Blood-Borne Infections
• Hepacivirus
• Substance Abuse, Intravenous/complications

• R01 AA030486 NIAAA NIH HHS
• R33 DA048439 NIDA NIH HHS
• R61 DA048439 NIDA NIH HHS

• Autophagy
• Chemoresistance
• Genetically engineered microbiota
• Immunomodulation
• Microbiota metabolites
• Multidisciplinary approach
• Outer membrane vesicles
• Tumor microbe microenvironment

• NAFLD
• alcohol‐related liver disease
• cirrhosis
• epidemiology
• natural history

• Humans
• Non-alcoholic Fatty Liver Disease/diagnosis
• Non-alcoholic Fatty Liver Disease/epidemiology
• Non-alcoholic Fatty Liver Disease/etiology
• Metabolic Syndrome/etiology
• Metabolic Syndrome/complications
• Liver Cirrhosis/etiology
• Liver Cirrhosis/complications
• Risk Factors
• Alcohol Drinking/adverse effects
• Alcohol Drinking/epidemiology

• MSD
• The Swedish Cancer Society
• Intercept Pharmaceuticals
• Gilead Sciences
• Echosens
• The Swedish Research Council
• Radiumhemmet Research Foundation and Region Stockholm
• Pfizer
• Astra Zeneca

• hepatitis B
• hepatitis C
• hepatocellular carcinoma
• meta-analysis
• smoking

• Humans
• Carcinoma, Hepatocellular/epidemiology
• Carcinoma, Hepatocellular/etiology
• Liver Neoplasms/epidemiology
• Liver Neoplasms/etiology
• Smoking/epidemiology
• Smoking/adverse effects
• Hepatitis C/epidemiology
• Hepatitis C/complications
• Hepatitis B/epidemiology
• Hepatitis B/complications
• Risk Factors
• Coinfection/epidemiology

• HBV
• HCV
• NAFLD
• alcohol consumption
• chronic liver disease
• viral hepatitis

• alcohol-related liver disease
• hepatocellular carcinoma
• miRNAs-based therapeutics
• microRNAs

• Convention_2021_ESR_11 Métropole Européenne de Lille
• Arreté n° 22000953 Région Hauts-de-France-Dispositif StaRs-Arreté n° 22000953
• n.a Ligue contre le cancer-Septentrion
• ANR CPJ_Sobolewski Agence Nationale pour la Recherche

• hepatocellular carcinoma
• locoregional therapy
• systemic therapy

• R01 CA240607 NCI NIH HHS
• R37 CA215427 NCI NIH HHS

• alcohol
• chronic liver disease
• cirrhosis
• liver transplantation
• organ failure
• viral hepatitis

• BFP/GRG/HSS/21/033 Ministry of Education, Research, and Innovation, Oman

• hepatocellular carcinoma
• liver cancer
• racial disparity
• therapeutic outcomes

• Male
• Humans
• Female
• Carcinoma, Hepatocellular/epidemiology
• Carcinoma, Hepatocellular/therapy
• Liver Neoplasms/epidemiology
• Liver Neoplasms/therapy
• Prevalence
• Hepatitis B/complications
• Hepatitis B/genetics
• Hepatitis C/complications
• Hepatitis C/epidemiology
• Treatment Outcome

• Molecular physiology
• Stem cells research

• I01 BX001991 BLRD VA
• R24 AA012885 NIAAA NIH HHS
• R01 AA018857 NIAAA NIH HHS
• P50 AA011999 NIAAA NIH HHS
• P30 CA014089 NCI NIH HHS
• R01 AA025204 NIAAA NIH HHS
• P30 DK048522 NIDDK NIH HHS
• U01 AA027681 NIAAA NIH HHS
• IK6 BX004205 BLRD VA
• R21 AA025470 NIAAA NIH HHS

• cardiovascular disease
• fatty liver
• hepatocellular carcinoma
• smoking

• 2022 Soonchunhyang University

Neoplasms contain tumor-initiating stem-like cells (TICs) that are characterized by increased drug resistance. The incidence of many cancer types have trended downward except for few cancer types, including hepatocellular carcinoma (HCC). Therefore mechanism of HCC development and therapy resistance needs to be understood. These multiple hits by hepatitis C virus (HCV) eventually promotes transformation and TIC genesis, leading to HCC development. This review article describes links between HCV-associated HCC and TICs. This review discusses 1) how HCV promotes genesis of TICs and HCC development; 2) how this process avails itself as a novel therapeutic target for HCC treatment; and 3) ten hall marks of TIC oncogenesis and HCC development as targets for novel therapeutic modalities.

Chronic Hepatitis B is a highly prevalent disease worldwide and is estimated to cause more than 800000 annual deaths from complications such as cirrhosis and hepatocellular carcinoma (HCC). Although universal hepatitis B vaccination programs may have reduced the incidence and prevalence of chronic hepatitis B and related HCC, the disease still imposes a significant healthcare burden in many endemic regions such as Africa and the Asia-Pacific region. This is especially concerning given the global underdiagnosis of hepatitis B and the limited availability of vaccination, screening, and treatment in low-resource regions. Demographics including male gender, older age, ethnicity, and geographic location as well as low socioeconomic status are more heavily impacted by chronic hepatitis B and related HCC. Methods to mitigate this impact include increasing screening in high-risk groups according to national guidelines, increasing awareness and health literacy in vulnerable populations, and developing more robust vaccination programs in under-served regions.

• Hepatitis B
• Epidemiology
• Hepatocellular carcinoma
• Socioeconomic status
• Healthcare disparity
• Hepatitis B vaccine

• Carcinoma, Hepatocellular/epidemiology
• Carcinoma, Hepatocellular/etiology
• Carcinoma, Hepatocellular/prevention & control
• Hepatitis B/complications
• Hepatitis B/diagnosis
• Hepatitis B/epidemiology
• Hepatitis B virus
• Hepatitis B, Chronic/complications
• Hepatitis B, Chronic/diagnosis
• Hepatitis B, Chronic/epidemiology
• Humans
• Liver Neoplasms
• Male
• Risk Factors
• Socioeconomic Factors

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.

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

• HBc
• HBs
• HBx
• hepatitis B virus
• hepatocellular carcinoma

• hepatitis B virus
• hepatitis C virus
• hepatocellular carcinoma
• metabolic syndrome
• visceral adipose tissue

• C-reactive protein
• X-ray repair cross-complementing group 1
• hepatic carcinoma
• interleukin-6
• polymerase chain reaction

• Alcohol
• Aspirin
• Coffee
• Diet
• Hepatocellular carcinoma
• Lifestyle
• Non-alcoholic fatty liver disease
• Non-alcoholic steatohepatitis
• Physical activity
• Prevention
• Probiotics
• Statins

Multiple meta-analyses and observational studies have reported that alcohol is a risk factor for liver cancer. However, whether there is a safe level of alcohol consumption remains unclear. We performed a systematic review and meta-analysis of the correlation between low-level alcohol consumption and the risk of liver cancer.

Nested case-control studies and cohort studies involving the general population published prior to July 2019 were searched. In total, 28 publications (31 cohorts) with 4,899 incident cases and 10,859 liver cancer-related deaths were included. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.

Compared with those with low levels of alcohol consumption, moderate and heavy drinkers (≥1 drink/day for females and ≥2 drinks/day for males) had pooled ORs of 1.418 (95% CI, 1.192 to 1.687; p<0.001) for liver cancer incidence and 1.167 (95% CI, 1.056 to 1.290; p=0.003) for liver cancer mortality. The pooled OR for liver disease-related mortality for those with more than low levels of alcohol consumption was 3.220 (95% CI, 2.116 to 4.898; p<0.001) and that for all-cause mortality was 1.166 (95% CI, 1.065 to 1.278; p=0.001). The sensitivity analysis showed that none of the studies had a strong effect on the pooled OR. The Egger test, Begg rank correlation test, and the funnel plot showed no overt indication of publication bias.

Continuous consumption of more than a low-level of alcohol (≥1 drink/day for females and ≥2 drinks/day for males) is related to a higher risk of liver cancer.

• Alcohol
• Liver neoplasms
• Meta-analysis
• Risk factors
• Systematic review

Liver cancer incidence in the United States is higher among African Americans compared to White Americans. The determinants of racial disparities in liver cancer incidence are not clear. Using data from White and African Americans from low socioeconomic backgrounds, we compared the prevalence of known liver cancer risk factors by race and assessed factors associated with liver cancer incidence. Understanding liver cancer risk differences can assist prevention strategies that target people at high risk, potentially based on risk factors that differ by race.

The purpose of this study was to examine differences in risk factors associated with hepatocellular carcinoma (HCC) among White and African Americans from low socioeconomic backgrounds in the Southern Community Cohort Study (SCCS). The SCCS is a prospective cohort study with participants from the southeastern US. HCC incidence rates were calculated. Multivariable Cox regression was used to calculate HCC-adjusted hazard ratios (aHR) associated with known baseline HCC risk factors for White and African Americans, separately. There were 294 incident HCC. The incidence rate ratio for HCC was higher (IRR = 1.4, 95%CI: 1.1–1.9) in African Americans compared to White Americans. White Americans saw a stronger association between self-reported hepatitis C virus (aHR = 19.24, 95%CI: 10.58–35.00) and diabetes (aHR = 3.55, 95%CI: 1.96–6.43) for the development of HCC compared to African Americans (aHR = 7.73, 95%CI: 5.71–10.47 and aHR = 1.48, 95%CI: 1.06–2.06, respectively) even though the prevalence of these risk factors was similar between races. Smoking (aHR = 2.91, 95%CI: 1.87–4.52) and heavy alcohol consumption (aHR = 1.59, 95%CI: 1.19–2.11) were significantly associated with HCC risk among African Americans only. In this large prospective cohort, we observed racial differences in HCC incidence and risk factors associated with HCC among White and African Americans.

• SCCS
• cancer risk
• racial disparity
• southeast

• U01 CA202979 NIH HHS
• R00 CA207848 NCI NIH HHS
• R01 CA092447 NCI NIH HHS
• R01 CA092447 NIH HHS
• K07 CA225404 NCI NIH HHS

• Animal model
• HCC subclasses
• Hepatocellular carcinoma
• Hyperglycemia
• Streptozotocin

• Hepatocellular carcinoma (HCC)
• liver transplant
• resection
• trans arterial chemoembolization (TACE)

• HBV-related hepatocellular carcinoma
• INTS10
• gene-environment interaction
• genetic risk score
• single-nucleotide polymorphism

• composite score of healthy lifestyle factors
• hepatocellular carcinoma risk

• Aged
• Carcinoma, Hepatocellular/epidemiology
• Carcinoma, Hepatocellular/prevention & control
• Female
• Follow-Up Studies
• Healthy Lifestyle
• Humans
• Liver Neoplasms/epidemiology
• Liver Neoplasms/prevention & control
• Male
• Prospective Studies
• Risk Assessment
• Risk Factors
• Singapore/epidemiology

• P30 CA047904 NCI NIH HHS
• R01 CA144034 NCI NIH HHS
• U01 CA182876 NCI NIH HHS
• UM1 CA182876 NCI NIH HHS

• deep learning
• hepatitis
• liver cancer

• ER stress
• Golgi
• HBV
• acetaldehyde
• hepatocytes

• Acetaldehyde
• Antigen Presentation/drug effects
• Endoplasmic Reticulum Stress/drug effects
• Endoplasmic Reticulum Stress/genetics
• Gene Expression/drug effects
• Golgi Apparatus/drug effects
• Golgi Apparatus/ultrastructure
• HLA-A2 Antigen/analysis
• Hep G2 Cells
• Hepatitis B virus/genetics
• Hepatitis B virus/immunology
• Histocompatibility Antigens Class I/drug effects
• Histocompatibility Antigens Class I/immunology
• Humans
• Liver/immunology
• Liver/virology
• RNA, Messenger/analysis
• Transfection
• Unfolded Protein Response/drug effects
• Unfolded Protein Response/genetics

• I01 BX004053 BLRD VA
• 1K01AA026864 HHS | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAA)
• K01 AA026864 NIAAA NIH HHS
• R01 AA027242 NIAAA NIH HHS
• R01 AA026723 NIAAA NIH HHS
• R01 AA027189 NIAAA NIH HHS

• Diabetes mellitus
• End stage liver disease
• Insulin resistance
• Liver cirrhosis
• Liver diseases
• Non-alcoholic fatty liver disease

• HBV
• HIV
• alcohol
• infectious agents
• neutrophil extracellular traps
• smoking

• Alcoholism/etiology
• Congresses as Topic
• Ethanol/toxicity
• Humans
• Life Style
• Risk Factors

• U01 AA026933 NIAAA NIH HHS
• K01 AA026864 NIAAA NIH HHS
• R01 CA228524 NCI NIH HHS
• R01 AA012863 NIAAA NIH HHS
• R01 AA026723 NIAAA NIH HHS
• UH2 AA026198 NIAAA NIH HHS
• UH2 AA026226 NIAAA NIH HHS
• I01 BX004053 BLRD VA
• R01 AA011576 NIAAA NIH HHS
• P60 AA009803 NIAAA NIH HHS
• P30 DK034854 NIDDK NIH HHS
• R01 AA017729 NIAAA NIH HHS
• R01 AA027189 NIAAA NIH HHS
• P01 CA217798 NCI NIH HHS
• R21 AA026428 NIAAA NIH HHS

Upregulation of Brf1 (TFIIB-related factor 1) and Pol III gene (RNA polymerase III-dependent gene, such as tRNAs and 5S rRNA) activities is associated with cell transformation and tumor development. Alcohol intake causes liver injury, such as steatosis, inflammation, fibrosis, and cirrhosis, which enhances the risk of HCC development. However, the mechanism of alcohol-promoted HCC remains to be explored. We have designed the complementary research system, which is composed of cell lines, an animal model, human samples, and experiments in vivo and in vitro, to carry out this project by using molecular biological, biochemical, and cellular biological approaches. It is a unique system to explore the mechanism of alcohol-associated HCC. Our results indicate that alcohol upregulates Brf1 and Pol III gene (tRNAs and 5S rRNA) transcription in primary mouse hepatocytes, immortalized mouse hepatocyte-AML-12 cells, and engineered human HepG2-ADH cells. Alcohol activates MSK1 to upregulate expression of Brf1 and Pol III genes, while inhibiting MSK1 reduces transcription of Brf1 and Pol III genes in alcohol-treated cells. The inhibitor of MSK1, SB-747651A, decreases the rates of cell proliferation and colony formation. Alcohol feeding promotes liver tumor development of the mouse. These results, for the first time, show the identification of the alcohol-response promoter fragment of the Pol III gene key transcription factor, Brf1. Our studies demonstrate that Brf1 expression is elevated in HCC tumor tissues of mice and humans. Alcohol increases cellular levels of Brf1, resulting in enhancement of Pol III gene transcription in hepatocytes through MSK1. Our mechanism analysis has demonstrated that alcohol-caused high-response fragment of the Brf1 promoter is at p-382/+109bp. The MSK1 inhibitor SB-747651A is an effective reagent to repress alcohol-induced cell proliferation and colony formation, which is a potential pharmaceutical agent. Developing this inhibitor as a therapeutic approach will benefit alcohol-associated HCC patients.

Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world. Previous studies have identified the importance of alcohol and hepatitis B (HBV) infection on HCC carcinogenesis, indicating synergy in the methods by which these etiologies advance cancer. However, the specific molecular mechanism behind alcohol and HBV-mediated carcinogenesis remains unknown. Because the microbiome is emerging as a potentially important regulator of cancer development, this study aims to classify the effects of HBV and alcohol on the intratumoral liver microbiome. RNA-sequencing data from The Cancer Genome Atlas (TCGA) were used to infer microbial abundance. This abundance was then correlated to clinical variables and to cancer and immune-associated gene expression, in order to determine how microbial abundance may contribute to differing cancer progression between etiologies. We discovered that the liver microbiome is likely oncogenic after exposure to alcohol or HBV, although these etiological factors could decrease the abundance of a few oncogenic microbes, which would lead to a tumor suppressive effect. In HBV-induced tumors, this tumor suppressive effect was inferred based on the downregulation of microbes that induce cancer and stem cell pathways. Alcohol-induced tumors were observed to have distinct microbial profiles from HBV-induced tumors, and different microbes are clinically relevant in each cohort, suggesting that the effects of the liver microbiome may be different in response to different etiological factors. Collectively, our data suggest that HBV and alcohol operate within a normally oncogenic microbiome to promote tumor development, but are also able to downregulate certain oncogenic microbes. Insight into why these microbes are downregulated following exposure to HBV or alcohol, and why the majority of oncogenic microbes are not downregulated, may be critical for understanding whether a pro-tumor liver microbiome could be suppressed or reversed to limit cancer progression.

• TCGA
• alcohol
• hepatitis B
• hepatocellular carcinoma
• microbiome

The aim of this study was to investigate the prognostic significance of preoperative AAPR in hepatitis B virus-related hepatocellular carcinoma patients after curative hepatectomy.

A total of 221 patients with hepatitis B virus-related HCC patients who received curative liver resection were included. After propensity matching analysis, 188 patients were enrolled in the final analysis. COX regression analyses were used to analyze the prognosis value of AAPR and other prognostic factors. The overall survival (OS) and recurrence-free survival (RFS) curves were constructed and compared between different groups.

The optimal cutoff of AAPR was defined as 0.40 with X-tile software. According to cutoff value, patients were divided into low-AAPR group (≤0.40) and high-AAPR group (>0.40). The cumulative 1-, 3-, and 5-year OS rates were 97.1%, 78.2%, and 67.3% in patients with AAPR>0.40 group, respectively, which were significantly higher than those in the AAPR≤0.40 group (80.2%, 54.4%, and 40.1%, respectively) (P <0.001). In the multivariate COX regression analysis, AAPR, tumor number, ascites, and portal vein tumor thrombus (PVTT) were independent risk factors for OS and RFS.

AAPR shows promise as a reliable prognostic factor in patients with hepatitis B virus-related HCC after curative hepatectomy, which could be used as a routine inspection of HCC patients before surgery.

• albumin-to-alkaline phosphatase ratio
• hepatitis B virus
• hepatocellular carcinoma
• prognosis

• Alcohol
• Cancer stem cells
• HCC
• NUMB
• Tumor-initiating stem-like cells (TICs)
• lncRNA

Hepatitis B virus (HBV) and alcohol abuse often contribute to the development of end-stage liver disease. Alcohol abuse not only causes rapid progression of liver disease in HBV infected patients but also allows HBV to persist chronically. Importantly, the mechanism by which alcohol promotes the progression of HBV-associated liver disease are not completely understood. Potential mechanisms include a suppressed immune response, oxidative stress, endoplasmic reticulum and Golgi apparatus stresses, and increased HBV replication. Certainly, more research is necessary to gain a better understanding of these mechanisms such that treatment(s) to prevent rapid liver disease progression in alcohol-abusing HBV patients could be developed. In this review, we discuss the aforementioned factors for the higher risk of liver diseases in alcohol-induced HBV pathogenies and suggest the areas for future studies in this field.

• Hepatitis B virus
• Alcohol
• Immunity
• Oxidative stress
• Liver disease

• Alcohol Drinking
• Alcoholism/complications
• Disease Progression
• End Stage Liver Disease/pathology
• Endoplasmic Reticulum/drug effects
• Gastrointestinal Microbiome
• Golgi Apparatus/drug effects
• Hepatitis B virus
• Hepatitis B, Chronic/complications
• Hepatitis B, Chronic/immunology
• Hepatitis B, Chronic/physiopathology
• Histocompatibility Antigens Class I
• Histocompatibility Antigens Class II
• Humans
• Liver/pathology
• Oxidative Stress
• Virus Replication

• HCC
• HCV
• Obesity
• Risk factors

• animal models
• hepatocellular carcinoma
• prevention

Hepatitis C Virus (HCV) mainly infects liver hepatocytes and replicates its single-stranded plus strand RNA genome exclusively in the cytoplasm. Viral proteins and RNA interfere with the host cell immune response, allowing the virus to continue replication. Therefore, in about 70% of cases, the viral infection cannot be cleared by the immune system, but a chronic infection is established, often resulting in liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Induction of cancer in the host cells can be regarded to provide further advantages for ongoing virus replication. One adaptation in cancer cells is the enhancement of cellular carbohydrate flux in glycolysis with a reduction of the activity of the citric acid cycle and aerobic oxidative phosphorylation. To this end, HCV downregulates the expression of mitochondrial oxidative phosphorylation complex core subunits quite early after infection. This so-called aerobic glycolysis is known as the “Warburg Effect” and serves to provide more anabolic metabolites upstream of the citric acid cycle, such as amino acids, pentoses and NADPH for cancer cell growth. In addition, HCV deregulates signaling pathways like those of TNF-β and MAPK by direct and indirect mechanisms, which can lead to fibrosis and HCC.

• ATP-Synthase
• HCC
• HCV
• NADH-ubiquinone oxidoreductase
• cytochrome c oxidase
• fibrosis
• hepatocellular carcinoma
• mitochondrial respiratory chain
• oxidative phosphorylation
• warburg effect

This study was designed to investigate the mechanism by which miR-129-5p affects the biological function of liver cancer cells. The expression levels of miR-129–5p in liver cancer tissues and cells were, respectively, determined. Crystal violet staining and flow cytometry were used to detect cell proliferation and apoptosis. Wound healing assay and transwell assay were performed to test cell migration and invasion. The target gene of miR-129–5p was analyzed and verified by bioinformatics analysis and luciferase reporter assay. Tumorigenicity assays in nude mice were used to test the antitumor ability of calcium calmodulin-dependent protein kinase IV (CAMK4). miR-129–5p was found to be underexpressed in hepatocellular cancer tissues and cells and also to inhibit liver cells proliferation, migration, and invasion and promote apoptosis. CAMK4 was a direct target for miR-129–5p and was lowly expressed in liver cancer tissues and cells. CAMK4 was also found to inhibit liver cells proliferation, migration and invasion, and promote apoptosis. CAMK4 might exert an antitumor effect by inhibiting the activation of mitogen-activated protein kinase (MAPK). MiR-129–5p was a tumor suppressor with low expression in liver cancer tissues and cells. CAMK4, which is a direct target gene of miR-129–5p, could inhibit tumor by inhibiting the activation of MAPK signaling pathway.