• All-cause mortality
• Direct-acting antiviral
• Hepatitis C
• Hepatocellular carcinoma
• Liver decompensation

• Humans
• Antiviral Agents/therapeutic use
• Carcinoma, Hepatocellular/mortality
• Carcinoma, Hepatocellular/virology
• Hepatitis C/drug therapy
• Hepatitis C/complications
• Liver Cirrhosis/drug therapy
• Liver Neoplasms/mortality
• Liver Transplantation
• Neoplasm Recurrence, Local/prevention & control

• Liver cirrhosis
• Mitochondria
• Nrf2/heme oxygenase-1
• Oxidative stress
• Redox homeostasis
• Regulatory T cells

• Animals
• Mice
• Antioxidants
• T-Lymphocytes, Regulatory
• NF-E2-Related Factor 2
• Liver Diseases/etiology
• Liver Cirrhosis

• 211113/Z/18/Z Wellcome Trust
• MR/S001581/1 Medical Research Council
• RG/13/11/30384 British Heart Foundation
• RG/20/3/34823 British Heart Foundation

• aggregation-induced emission
• carbon radicals
• photothermal therapy
• the second near-infrared window
• thermodynamic therapy

• Humans
• Phototherapy
• Heterografts
• Nanoparticles/chemistry
• Fluorescent Dyes/chemistry
• Mouth Neoplasms/therapy

• 8217102092 National Natural Science Foundation of China
• 81772889 National Natural Science Foundation of China
• 52073139 National Natural Science Foundation of China
• 202042 Scientific Research Project of Shenzhen Pingshan District Health System
• High Level Introduction of Talent Research Startup Fund
• Southern Hospital
• Nanfang Medical University
• National Natural Science Foundation of China

Chronic inflammation due to hepatitis C virus (HCV) infection leads to liver fibrosis and rearrangement of liver tissue, which is responsible for the development of portal hypertension (PH) and hepatocellular carcinoma (HCC). The advent of direct-acting antiviral drugs has revolutionized the natural history of HCV infection, providing an overall eradication rate of over 90%. Despite a significant decrease after sustained virological response (SVR), the rate of HCC and liver-related complications is not completely eliminated in patients with advanced liver disease. Although the reasons are still unclear, cirrhosis itself has a residual risk for the development of HCC and other PH-related complications. Ultrasound elastography is a recently developed non-invasive technique for the assessment of liver fibrosis. Following the achievement of SVR, liver stiffness (LS) usually decreases, as a consequence of reduced inflammation and, possibly, fibrosis. Recent studies emphasized the application of LS assessment in the management of patients with SVR in order to define the risk for developing the complications of chronic liver disease (functional decompensation, gastrointestinal bleeding, HCC) and to optimize long-term prognostic outcomes in clinical practice.

• Direct-acting antiviral agents
• Liver stiffness
• Portal hypertension
• Hepatocellular carcinoma

• Chronic hepatitis C virus
• FIB-4 score
• predictor
• sofosbuvir-based regimens
• transient elastography

• Cell survival
• Cellular stress
• Hepatitis C virus
• Selective autophagy

• 4-Hydroxy-2-nonenal (HNE)
• Disease
• Immunohistochemistry
• Lipid peroxidation
• Monoclonal antibodies
• Oxidative stress
• Pathology
• Pathophysiology

• Aldehydes/metabolism
• Amyloid beta-Peptides/chemistry
• Amyloid beta-Peptides/metabolism
• Animals
• Biomarkers/metabolism
• Cardiovascular Diseases/metabolism
• Cardiovascular Diseases/pathology
• Fatty Acids, Unsaturated/metabolism
• Humans
• Immunohistochemistry
• Lipid Peroxidation
• Lung Diseases/metabolism
• Lung Diseases/pathology
• Neoplasms/metabolism
• Neoplasms/pathology
• Neurodegenerative Diseases/metabolism
• Neurodegenerative Diseases/pathology
• Oxidative Stress
• Reactive Oxygen Species/metabolism
• tau Proteins/chemistry
• tau Proteins/metabolism

• Chronic liver fibrosis
• Hyperoside
• Nrf2
• Oxidative stress

• ALT, alanine transaminases
• APRI, AST to Platelet ratio index
• AST, aspartate transaminases
• BMI, body mass index
• CHB, chronic hepatitis B
• CLD, chronic liver disease
• DM, diabetes mellitus
• ETR, end of treatment response
• EVR, early virological response
• FIB4, fibrosis-4 score
• HCV, hepatitis C
• IQR/M, interquartile range/median
• LB, liver biopsy
• LF, liver fibrosis
• LSM, liver stiffness measurement
• NPV, negative predictive value
• PEG INF, Pegylated Interferon
• PPV, positive predictive value
• RBV, Ribavarin
• RGT, response guided treatment
• ROC, receiver operating characteristic
• RVR, rapid virological response
• SVR, sustained virological response
• TE, transient elastography
• chronic hepatitis C
• kPa, kilopascals
• liver biopsy
• liver fibrosis
• noninvasive markers
• transient elastography

• Hepatitis virus
• Innate immunity
• Mitochondrial fission and fusion
• Mitophagy
• Virus

• Animals
• Autophagy
• Humans
• Mitochondria/genetics
• Mitochondria/metabolism
• Mitochondria/pathology
• Mitochondrial Dynamics
• Mitophagy
• Virus Diseases/metabolism
• Virus Diseases/pathology

• AI085087 NIAID NIH HHS
• R01 AI139234 NIAID NIH HHS
• R01 AI085087 NIAID NIH HHS
• R56 AI085087 NIAID NIH HHS
• DK08379 NIDDK NIH HHS
• R01 DK077704 NIDDK NIH HHS
• DK077704 NIDDK NIH HHS

Hepatocellular carcinoma (HCC) has been known as one of the most lethal human malignancies, due to the difficulty of early detection, chemoresistance, and radioresistance, and is characterized by active angiogenesis and metastasis, which account for rapid recurrence and poor survival. Its development has been closely associated with multiple risk factors, including hepatitis B and C virus infection, alcohol consumption, obesity, and diet contamination. Genetic alterations and genomic instability, probably resulted from unrepaired DNA lesions, are increasingly recognized as a common feature of human HCC. Dysregulation of DNA damage repair and signaling to cell cycle checkpoints, known as the DNA damage response (DDR), is associated with a predisposition to cancer and affects responses to DNA-damaging anticancer therapy. It has been demonstrated that various HCC-associated risk factors are able to promote DNA damages, formation of DNA adducts, and chromosomal aberrations. Hence, alterations in the DDR pathways may accumulate these lesions to trigger hepatocarcinogenesis and also to facilitate advanced HCC progression. This review collects some of the most known information about the link between HCC-associated risk factors and DDR pathways in HCC. Hopefully, the review will remind the researchers and clinicians of further characterizing and validating the roles of these DDR pathways in HCC.

Hepatitis C virus (HCV) has become a major public health issue. It is prevalent in most countries. HCV infection frequently begins without clinical symptoms, before progressing to persistent viremia, chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) in the majority of patients (70% to 80%). Alcohol is an independent cofactor that accelerates the development of HCC in chronic hepatitis C patients. The purpose of the current study was to evaluate ethanol-induced hepatic changes in HCV core-Tg mice and mutant core Tg mice. Wild type (NTG), core wild-Tg mice (TG-K), mutant core 116-Tg mice (TG-116) and mutant core 99-Tg mice (TG-99) were used in this investigation. All groups were given drinking water with 10% ethanol and 5% sucrose for 13 weeks. To observe liver morphological changes, we performed histopathological and immunohistochemical examinations. Histopathologically, NTG, TG-K and TG-116 mice showed moderate centrilobular necrosis, while severe centrilobular necrosis and hepatocyte dissociation were observed in TG-99 mice with increasing lymphocyte infiltration and piecemeal necrosis. In all groups, a small amount of collagen fiber was found, principally in portal areas. None of the mice were found to have myofibroblasts based on immunohistochemical staining specific for α-SMA. CYP2E1-positive cells were clearly detected in the centrilobular area in all groups. In the TG-99 mice, we also observed cells positive for CK8/18, TGF-β1 and phosphorylated (p)-Smad2/3 and p21 around the necrotic hepatocytes in the centrilobular area (p < 0.01). Based on our data, alcohol intake induced piecemeal necrosis and hepatocyte dissociation in the TG-99 mice. These phenomena involved activation of the TGF-β1/p-Smad2/3/p21 signaling pathway in hepatocytes. Data from this study will be useful for elucidating the association between alcohol intake and HCV infection.

• N01AI40038 NIAID NIH HHS
• R24 AA012885 NIAAA NIH HHS
• RC2 AA019392 NIAAA NIH HHS
• R01 AA018857 NIAAA NIH HHS
• P30 DK048522 NIDDK NIH HHS
• R21 AA025470 NIAAA NIH HHS
• P30 CA014089 NCI NIH HHS
• R01 AA025204 NIAAA NIH HHS
• R01 CA108302 NCI NIH HHS
• P50 AA011999 NIAAA NIH HHS

To investigate the effect of blueberry juice intake on rat liver fibrosis and its influence on hepatic antioxidant defense.

Rabbiteye blueberry was used to prepare fresh juice to feed rats by daily gastric gavage. Dan-shao-hua-xian capsule (DSHX) was used as a positive control for liver fibrosis protection. Liver fibrosis was induced in male Sprague-Dawley rats by subcutaneous injection of CCl₄ and feeding a high-lipid/low-protein diet for 8 weeks. Hepatic fibrosis was evaluated by Masson staining. The expression of α-smooth muscle actin (α-SMA) and collagen III (Col III) were determined by immunohistochemical techniques. The activities of superoxide dismutase (SOD) and malondialdehyde (MDA) in liver homogenates were determined. Metallothionein (MT) expression was detected by real-time RT-PCR and immunohistochemical techniques.

Blueberry juice consumption significantly attenuates CCl₄-induced rat hepatic fibrosis, which was associated with elevated expression of metallothionein (MT), increased SOD activity, reduced oxidative stress, and decreased levels of α-SMA and Col III in the liver.

Our study suggests that dietary supplementation of blueberry juice can augment antioxidative capability of the liver presumably via stimulating MT expression and SOD activity, which in turn promotes HSC inactivation and thus decreases extracellular matrix collagen accumulation in the liver, and thereby alleviating hepatic fibrosis.

• Actins/genetics
• Actins/metabolism
• Animals
• Beverages
• Blueberry Plants/chemistry
• Carbon Tetrachloride/adverse effects
• Collagen Type III/genetics
• Collagen Type III/metabolism
• Dietary Supplements
• Drugs, Chinese Herbal/administration & dosage
• Gene Expression
• Liver/drug effects
• Liver/metabolism
• Liver/pathology
• Liver Cirrhosis, Experimental/chemically induced
• Liver Cirrhosis, Experimental/metabolism
• Liver Cirrhosis, Experimental/prevention & control
• Male
• Malondialdehyde/metabolism
• Metallothionein/genetics
• Metallothionein/metabolism
• Rats
• Superoxide Dismutase/metabolism
• Up-Regulation

This study was designed to investigate the potentially protective effects of glycyrrhetinic acid (GA) and the role of transcription factor nuclear factor-erythroid 2(NF-E2)-related factor 2 (Nrf2) signaling in the regulation of Carbon Tetrachloride (CCl₄)-induced chronic liver fibrosis in mice. The potentially protective effects of GA on CCl₄-induced chronic liver fibrosis in mice were depicted histologically and biochemically. Firstly, histopathological changes including regenerative nodules, inflammatory cell infiltration and fibrosis were induced by CCl₄.Then, CCl₄ administration caused a marked increase in the levels of serum aminotransferases (GOT, GPT), serum monoamine oxidase (MAO) and lipid peroxidation (MDA) as well as MAO in the mice liver homogenates. Also, decreased nuclear Nrf2 expression, mRNA levels of its target genes such as superoxide dismutase 3 (SOD3), catalase (CAT), glutathione peroxidase 2 (GPX2), and activity of cellular antioxidant enzymes were found after CCl₄ exposure. All of these phenotypes were markedly reversed by the treatment of the mice with GA. In addition, GA exhibited the antioxidant effects in vitro by on FeCl₂-ascorbate induced lipid peroxidation in mouse liver homogenates, and on DPPH scavenging activity. Taken together, these results suggested that GA can protect the liver from oxidative stress in mice, presumably through activating the nuclear translocation of Nrf2, enhancing the expression of its target genes and increasing the activity of the antioxidant enzymes. Therefore, GA may be an effective hepatoprotective agent and viable candidate for treating liver fibrosis and other oxidative stress-related diseases.

• Animals
• Antioxidants/metabolism
• Ascorbic Acid/pharmacology
• Biphenyl Compounds/metabolism
• Chronic Disease
• Cytoprotection/drug effects
• Ferrous Compounds/pharmacology
• Fluorocarbons/toxicity
• Glycyrrhetinic Acid/pharmacology
• Lipid Peroxidation/drug effects
• Liver/drug effects
• Liver/enzymology
• Liver/metabolism
• Liver/pathology
• Liver Cirrhosis/chemically induced
• Liver Cirrhosis/genetics
• Liver Cirrhosis/metabolism
• Liver Cirrhosis/pathology
• Male
• Mice
• NF-E2-Related Factor 2/genetics
• Oxidative Stress/drug effects
• Picrates/metabolism
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• Up-Regulation/drug effects

AIM: To investigate the anti-oxidative and anti-fibrotic effects of aloe vera in patients with liver fibrosis.

METHODS: Aloe vera high molecular weight fractions (AHM) were processed by patented hyper-dry system in combination of freeze-dry technique with microwave and far infrared-ray radiation. Fifteen healthy volunteers as the control group and 40 patients were included. The patients were randomly subdivided into two equal groups: the conventional group was treated with placebo (starch), and AHM group was treated with 0.15 gm/d AHM, both for 12 consecutive weeks. The patients were investigated before and after treatment. Serum activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), hyaluronic acid (HA), transforming growth factor-β (TGF-β) and matrixmetalloproteinase-2 (MMP-2) were determined. The reduced glutathione (GSH) and malondialdehyde (MDA) levels in liver were assayed and the expression of hepatic α-smooth muscle actin (α-SMA) was identified by immunohistochemistry.

RESULTS: At the start of the study, the hematoxylin and eosin staining revealed fibro-proliferated bile ductules, thick fibrous septa and dense inflammatory cellular infiltration in the patients before treatment. The use of AHM for 12 wk significantly ameliorated the fibrosis, inhibited the inflammation, and resulted in minimal infiltration and minimal fibrosis compared to the conventional group. The enzyme activities of the liver (ALT, AST and ALP) were attenuated after treatment in both groups, and the decrease in the AHM group was more significant as compared with the conventional group. Similar to the AST, the MDA levels were significantly higher before treatment, and were attenuated after treatment in both groups. In contrast, the hepatic glutathione content in the patients were decreased significantly in the AHM group compared to the controls. The serum levels of the fibrosis markers (HA, TGF-β and MMP-2) were also reduced significantly after treatment. The expression of α-SMA was modified in patients before and after treatment as compared with the normal controls. In the conventional group, there was only thin and incomplete parenchymal α-SMA positive septum joining the thickened centrilobular veins, while in the AHM group, few α-SMA positive cells were present in sinusoid and lobule after treatment.

CONCLUSION: Oral supplementation with AHM could be helpful in alleviating the fibrosis and inflammation of hepatic fibrosis patients.

• Hepatic fine periportal fibrosis
• Aloe vera
• α-smooth muscle actin
• Transforming growth factor-β
• Hyaluronic acid

AIM: To determine the associations between leptin and ghrelin concentrations and sustained virological response (SVR) in chronic hepatitis C patients with steatosis.

METHODS: We retrospectively assessed 56 patients infected with hepatitis C virus (HCV) genotype-1 and 40 with HCV genotype-3. Patients with decompensated cirrhosis, and those with other causes of chronic liver disease, were excluded. Serum HCV-RNA concentrations were measured before the initiation of treatment; at weeks 12 (for genotype 1 patients), 24 and 48 during treatment; and 24 wk after the end of treatment. Genotype was determined using INNO-LIPA HCV assays, and serum leptin and ghrelin concentrations were measured using enzyme-linked immunosorbent assay. Biopsy specimens were scored according to the Ishak system and steatosis was graded as mild, moderate, or severe, according to the Brunt classification.

RESULTS: Overall, SVR was positively related to the presence of genotype-3, to biopsy-determined lower histological stage of liver disease, and lower grade of steatosis. Patients ≥ 40 years old tended to be less responsive to therapy. In genotype-1 infected patients, SVR was associated with a lower grade of liver steatosis, milder fibrosis, and an absence of insulin resistance. Genotype-1 infected patients who did not achieve SVR had significantly higher leptin concentrations at baseline, with significant increases as the severity of steatosis worsened, whereas those who achieved SVR had higher ghrelin concentrations. In genotype-3 infected patients, SVR was associated only with fibrosis stage and lower homeostasis model assessment insulin resistance at baseline, but not with the degree of steatosis or leptin concentrations. Genotype-3 infected patients who achieved SVR showed significant decreases in ghrelin concentration at end of treatment. Baseline ghrelin concentrations were elevated in responders of both genotypes who had moderate and severe steatosis.

CONCLUSION: Increased serum leptin before treatment may predict non-SVR, especially in HCV genotype-1 infected patients, whereas increased ghrelin may predict SVR in genotype-1.

• Hepatitis C virus
• Steatosis
• Leptin
• Ghrelin
• Sustained virological response

• Cell Death/drug effects
• Cell Line, Tumor
• DEAD Box Protein 58
• DEAD-box RNA Helicases/genetics
• DEAD-box RNA Helicases/metabolism
• Down-Regulation/drug effects
• Hepacivirus/drug effects
• Hepacivirus/metabolism
• Hepacivirus/physiology
• Host-Pathogen Interactions
• Humans
• Interferon-beta/pharmacology
• Liver/cytology
• Liver/drug effects
• Liver/metabolism
• Liver/virology
• Protein Binding/drug effects
• Receptors, Immunologic
• Signal Transduction/drug effects
• TNF-Related Apoptosis-Inducing Ligand/metabolism
• Toll-Like Receptors/genetics
• Toll-Like Receptors/metabolism
• Viral Envelope Proteins/metabolism
• Virus Replication/drug effects

• DK002958 NIDDK NIH HHS
• F31 AI071353 NIAID NIH HHS
• A1061158 PHS HHS
• F31AI071353 NIAID NIH HHS
• K24 CA139570 NCI NIH HHS
• K08 DK002958 NIDDK NIH HHS

• Cell Line
• Cell Proliferation/drug effects
• Drug Administration Routes
• Drug Compounding
• Hepacivirus/drug effects
• Hepacivirus/growth & development
• Humans
• Silybin
• Silymarin/administration & dosage
• T-Lymphocytes
• Virus Replication/drug effects

• AT002895 NCCIH NIH HHS
• R21 CA125321 NCI NIH HHS
• R21 AT002895 NCCIH NIH HHS
• R01 CA104286 NCI NIH HHS
• UL1 RR025014 NCRR NIH HHS

• c-jun
• liver cancer
• stat3
• hcv
• and nitric oxide

• Animals
• COP9 Signalosome Complex
• Carcinoma, Hepatocellular/virology
• DNA Repair
• Hepacivirus
• Humans
• Intracellular Signaling Peptides and Proteins/physiology
• Liver Neoplasms/virology
• Mice
• Mice, Transgenic
• Nitric Oxide/physiology
• Oxidation-Reduction
• Peptide Hydrolases/physiology
• STAT3 Transcription Factor/physiology
• Signal Transduction

• N01AI40038 NIAID NIH HHS
• CA108302 NCI NIH HHS
• P50AA11999 NIAAA NIH HHS
• P01CA123328 NCI NIH HHS
• R01 AA018857-02 NIAAA NIH HHS
• P01 CA123328 NCI NIH HHS
• 1R01 AA018857-01 NIAAA NIH HHS
• R01 AA018857 NIAAA NIH HHS
• R01 CA108302 NCI NIH HHS
• P50 AA011999 NIAAA NIH HHS

AIM: To investigate the effects of blueberry on hepatic fibrosis and NF-E2-related factor 2 (Nrf2) transcription factor in rats.

METHODS: Forty-five male Sprague-Dawley rats were randomly divided into control group (A); CCl₄-induced hepatic fibrosis group (B); blueberry prevention group (C); Dan-shao-hua-xian capsule (DSHX) prevention group (D); and blueberry + DSHX prevention group (E). Liver fibrosis was induced in rats by subcutaneous injection of CCl₄ and a high-lipid/low-protein diet for 8 wk (except the control group). The level of hyaluronic acid (HA) and alanine aminotransferase (ALT) in serum was examined. The activity of superoxide dismutase (SOD), glutathione-S-transferase (GST) and malondialdehyde (MDA) in liver homogenates was determined. The degree of hepatic fibrosis was evaluated by hematoxylin and eosin and Masson staining. Expression of Nrf2 and NADPH quinone oxidoreductase 1 (Nqo1) was detected by real-time reversed transcribed-polymerase chain reaction, immunohistochemical techniques, and western blotting.

RESULTS: Compared with group B, liver indices, levels of serum HA and ALT of groups C, D and E were reduced (liver indices: 0.038 ± 0.008, 0.036 ± 0.007, 0.036 ± 0.005 vs 0.054 ± 0.009, P < 0.05; HA: 502.33 ± 110.57 ng/mL, 524.25 ± 255.42 ng/mL, 499.25 ± 198.10 ng/mL vs 828.50 ± 237.83 ng/mL, P < 0.05; ALT: 149.44 ± 16.51 U/L, 136.88 ± 10.07 U/L, 127.38 ± 11.03 U/L vs 203.25 ± 31.62 U/L, P < 0.05), and SOD level was significantly higher, but MDA level was lower, in liver homogenates (SOD: 1.36 ± 0.09 U/mg, 1.42 ± 0.13 U/mg, 1.50 ± 0.15 U/mg vs 1.08 ± 0.19 U/mg, P < 0.05; MDA: 0.294 ± 0.026 nmol/mg, 0.285 ± 0.025 nmol/mg, 0.284 ± 0.028 nmol/mg vs 0.335 ± 0.056 nmol/mg, P < 0.05). Meanwhile, the stage of hepatic fibrosis was significantly weakened (P < 0.05). Compared with group A, the activity of GST liver homogenates and expression levels of Nrf2 and Nqo1 in group B were elevated (P < 0.05). The expression level of Nrf2 and Nqo1 in groups C, D, and E were increased as compared with group B, but the difference was not significant.

CONCLUSION: Blueberry has preventive and protective effects on CCl₄-induced hepatic fibrosis by reducing hepatocyte injury and lipid peroxidation. However, these effects may not be related to the activation of Nrf2 during long-term of CCl₄.

• Blueberry
• Hepatic fibrosis
• NF-E2-related factor 2
• NADPH quinone oxidoreductase 1
• Glutathione-S-transferase

• Adipokines/metabolism
• Animals
• Apoptosis
• Fatty Liver/immunology
• Fatty Liver/virology
• Hepacivirus/physiology
• Hepatic Stellate Cells/immunology
• Hepatic Stellate Cells/virology
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/immunology
• Humans
• Insulin Resistance
• Lipid Metabolism
• Liver Cirrhosis/immunology
• Liver Cirrhosis/virology
• Oxidative Stress
• T-Lymphocytes, Cytotoxic/immunology

• hcv
• hiv
• drug user
• inflammation
• cell death

• CD4 Antigens/immunology
• CD8 Antigens/immunology
• Cell Death
• Disease Progression
• HIV Infections/epidemiology
• Hepatitis C, Chronic/diagnosis
• Hepatitis C, Chronic/epidemiology
• Hepatitis C, Chronic/physiopathology
• Humans
• Inflammation/epidemiology
• Inflammation/immunology
• Inflammation/pathology
• Liver Cirrhosis/epidemiology
• Liver Cirrhosis/pathology
• Substance Abuse, Intravenous/epidemiology

• R01 HL087576 NHLBI NIH HHS
• R01 HL087576-01A1 NHLBI NIH HHS

• 8-Hydroxy-2'-Deoxyguanosine
• Aged
• Alanine Transaminase/metabolism
• Aldehydes/analysis
• Antigens, CD/metabolism
• Antigens, Differentiation, Myelomonocytic/metabolism
• Biomarkers, Tumor/metabolism
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/virology
• DNA Adducts
• DNA Damage
• Deoxyguanosine/analogs & derivatives
• Deoxyguanosine/analysis
• Female
• Follow-Up Studies
• Hepacivirus/pathogenicity
• Hepatectomy
• Hepatitis C/metabolism
• Hepatitis C/virology
• Humans
• Inflammation/metabolism
• Lipid Peroxidation
• Liver Neoplasms/metabolism
• Liver Neoplasms/pathology
• Liver Neoplasms/virology
• Male
• Microfilament Proteins/metabolism
• Middle Aged
• Neoplasm Recurrence, Local/diagnosis
• Neoplasm Recurrence, Local/etiology
• Oxidative Stress
• Prognosis
• Reactive Oxygen Species/metabolism
• Risk Factors
• Survival Rate
• Vesicular Transport Proteins/metabolism

• K22 ES11660 NIEHS NIH HHS
• P30 ES10126 NIEHS NIH HHS
• R01 ES12686 NIEHS NIH HHS
• U19 ES11391 NIEHS NIH HHS

• Adult
• Antiviral Agents/pharmacology
• Antiviral Agents/therapeutic use
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/virology
• Cell Line, Tumor
• Cells, Cultured
• Dose-Response Relationship, Drug
• Female
• Hepacivirus/pathogenicity
• Hepatitis C, Chronic/drug therapy
• Hepatitis C, Chronic/metabolism
• Hepatocytes/metabolism
• Hepatocytes/pathology
• Humans
• Male
• Middle Aged
• Monocytes/cytology
• Monocytes/metabolism
• NF-kappa B/antagonists & inhibitors
• NF-kappa B/drug effects
• NF-kappa B/metabolism
• Plant Extracts/pharmacology
• Plant Extracts/therapeutic use
• RNA, Viral/metabolism
• Signal Transduction/drug effects
• Signal Transduction/physiology
• Silymarin/pharmacology
• Silymarin/therapeutic use
• T-Lymphocytes/metabolism
• T-Lymphocytes/pathology
• Tumor Necrosis Factor-alpha/drug effects
• Tumor Necrosis Factor-alpha/metabolism

• R01 DK 62187 NIDDK NIH HHS
• R24-AT-00766 NCCIH NIH HHS
• U19 AI 66328 NIAID NIH HHS

• Animals
• Antioxidants/metabolism
• Gene Transfer Techniques
• Liver/pathology
• Liver/surgery
• Liver Transplantation
• Mice
• Oxidative Stress
• Rats
• Reperfusion Injury/prevention & control
• Superoxide Dismutase/genetics

• Antiviral Agents/therapeutic use
• Clinical Trials, Phase II as Topic
• Hepatitis C, Chronic/drug therapy
• Hepatitis C, Chronic/immunology
• Histamine/adverse effects
• Histamine/pharmacokinetics
• Histamine/therapeutic use
• Humans
• Oligonucleotides, Antisense/therapeutic use