• metabolic syndrome (mets)
• predictive power
• proportion
• ratio
• serum transaminases

• hepatic steatosis
• intracellular signaling
• non alcoholic fatty liver disease
• obesity

• liver biopsy
• new drug development
• nonalcoholic steatohepatitis
• value and challenges

• Biopsy
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/pathology
• Drug Development
• Humans
• Liver/pathology
• Liver Cirrhosis/pathology
• Liver Neoplasms/pathology
• Non-alcoholic Fatty Liver Disease/drug therapy
• Non-alcoholic Fatty Liver Disease/pathology
• Reproducibility of Results

Increased reactive oxidative stress, lipid peroxidation, inflammation, and fibrosis, which contribute to tissue damage and development and progression of nonalcoholic liver disease (NAFLD), play important roles in microcirculatory disorders. We investigated the effect of the modulatory properties of simvastatin (SV) on the liver and adipose tissue microcirculation as well as metabolic and oxidative stress parameters, including the advanced lipoxidation end product–receptors of advanced glycation end products (ALE-RAGE) pathway. SV was administered to an NAFLD model constructed using a high-fat–high-carbohydrate diet (HFHC). HFHC caused metabolic changes indicative of nonalcoholic steatohepatitis; treatment with SV protected the mice from developing NAFLD. SV prevented microcirculatory dysfunction in HFHC-fed mice, as evidenced by decreased leukocyte recruitment to hepatic and fat microcirculation, decreased hepatic stellate cell activation, and improved hepatic capillary network architecture and density. SV restored basal microvascular blood flow in the liver and adipose tissue and restored the endothelium-dependent vasodilatory response of adipose tissue to acetylcholine. SV treatment restored antioxidant enzyme activity and decreased lipid peroxidation, ALE-RAGE pathway activation, steatosis, fibrosis, and inflammatory parameters. Thus, SV may improve microcirculatory function in NAFLD by downregulating oxidative and ALE-RAGE stress and improving steatosis, fibrosis, and inflammatory parameters.

• adipose tissue
• liver
• microcirculation
• nonalcoholic fatty liver disease
• simvastatin

• NASH
• alcohol
• chemokines
• cholestasis
• cytokines
• drugs
• liver fibrosis
• therapy

• African Americans
• Diabetes
• Liver cancer
• Racial disparities

• Black or African American
• Cohort Studies
• Diabetes Mellitus/epidemiology
• Humans
• Liver Neoplasms/epidemiology
• Risk Factors
• White People

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

• MAFLD
• NAFLD
• epigenetics
• insulin resistance
• metabolic syndrome
• oxidative stress

• Thrombosis
• exercise
• hypercoagulable
• liver transplantation
• nonalcoholic steatohepatitis
• thromboembolic.

This study examines the effects of chicoric acid (CA) on nonalcoholic fatty liver disease (NAFLD) in high-fat-diet- (HFD-) fed C57BL/6 mice. CA treatment decreased body weight and white adipose weight, mitigated hyperglycemia and dyslipidemia, and reduced hepatic steatosis in HFD-fed mice. Moreover, CA treatment reversed HFD-induced oxidative stress and inflammation both systemically and locally in the liver, evidenced by the decreased serum malondialdehyde (MDA) abundance, increased serum superoxide dismutase (SOD) activity, lowered in situ reactive oxygen species (ROS) in the liver, decreased serum and hepatic inflammatory cytokine levels, and reduced hepatic inflammatory cell infiltration in HFD-fed mice. In addition, CA significantly reduced lipid accumulation and oxidative stress in palmitic acid- (PA-) treated HepG2 cells. In particular, we identified AMPK as an activator of Nrf2 and an inactivator of NFκB. CA upregulated AMPK phosphorylation, the nuclear protein level of Nrf2, and downregulated NFκB protein level both in HFD mice and PA-treated HepG2 cells. Notably, AMPK inhibitor compound C blocked the regulation of Nrf2 and NFκB, as well as ROS overproduction mediated by CA in PA-treated HepG2 cells, while AMPK activator AICAR mimicked the effects of CA. Similarly, Nrf2 inhibitor ML385 partly blocked the regulation of antioxidative genes and ROS overproduction by CA in PA-treated HepG2 cells. Interestingly, high-throughput pyrosequencing of 16S rRNA suggested that CA could increase Firmicutes-to-Bacteroidetes ratio and modify gut microbial composition towards a healthier microbial profile. In summary, CA plays a preventative role in the amelioration of oxidative stress and inflammation via the AMPK/Nrf2/NFκB signaling pathway and shapes gut microbiota in HFD-induced NAFLD.

• Atrial fibrillation
• Cardiovascular disease
• Cirrhosis
• Direct oral anticoagulants
• Fatty liver
• Heparin
• Liver disease
• Stroke
• Thrombosis
• Warfarin

• Administration, Oral
• Anticoagulants/adverse effects
• Anticoagulants/therapeutic use
• Atrial Fibrillation/drug therapy
• Humans
• Non-alcoholic Fatty Liver Disease/drug therapy
• Venous Thromboembolism/drug therapy

• advanced glycation end products
• microcirculation
• nonalcoholic fatty liver disease
• pyridoxamine

• Superb Microvascular Imaging
• breast
• carotid plaques
• liver
• skeletal muscle
• thyroid

• Breast/blood supply
• Breast/diagnostic imaging
• Carotid Arteries/diagnostic imaging
• Humans
• Liver/blood supply
• Liver/diagnostic imaging
• Microvessels/diagnostic imaging
• Muscle, Skeletal/blood supply
• Muscle, Skeletal/diagnostic imaging
• Plaque, Atherosclerotic/diagnostic imaging
• Thyroid Gland/blood supply
• Thyroid Gland/diagnostic imaging
• Ultrasonography/methods

Annonacin, an annonaceous acetogenin isolated from Annona muricata has been reported to be strongly cytotoxic against various cell lines, in vitro. Nevertheless, its effect against in vivo tumor promoting activity has not been reported yet. Therefore, this study was aimed to investigate antitumor-promoting activity of annonacin via in vivo two-stage mouse skin tumorigenesis model and its molecular pathways involved.

Mice were initiated with single dose of 7,12-dimethylbenz[α]anthracene (DMBA) (390 nmol/100 μL) followed by, in subsequent week, repeated promotion (twice weekly; 22 weeks) with 12-O-tetradecanoylphorbol-13-acetate (TPA) (1.7 nmol/100 μL). Annonacin (85 nM) and curcumin (10 mg/kg; reference) were, respectively, applied topically to DMBA/TPA-induced mice 30 min before each TPA application for 22 weeks. Upon termination, histopathological examination of skin, liver and kidney as well as genes and proteins expression analysis were conducted to elucidate the potential mechanism of annonacin.

With comparison to the carcinogen control, Annonacin significantly increased the tumor latency period and reduced the tumor incidence, tumor burden and tumor volume, respectively. In addition, it also suppressed tumorigenesis manifested by significant reduction of hyperkeratosis, dermal papillae and number of keratin pearls on skin tissues. Annonacin also appeared to be non-toxic to liver and kidney. Significant modulation of both AKT, ERK, mTOR, p38, PTEN and Src genes and proteins were also observed in annonacin-targeted signaling pathway(s) against tumorigenesis.

Collectively, results of this study indicate that annonacin is a potential therapeutic compound targeting tumor promoting stage in skin tumorigenesis by modulating multiple gene and protein in cancer signaling pathways without apparent toxicity.

The online version of this article (10.1186/s12906-019-2650-1) contains supplementary material, which is available to authorized users.

• Annonacin
• Antitumor promotion
• Gene expression
• Skin tumorigenesis

• Contrast-enhanced ultrasound
• Fatty liver progression
• Non-alcoholic steatohepatitis

• Animals
• Contrast Media
• Disease Models, Animal
• Disease Progression
• Image Enhancement/methods
• Liver/diagnostic imaging
• Liver/pathology
• Male
• Mice
• Mice, Inbred C57BL
• Non-alcoholic Fatty Liver Disease/diagnostic imaging
• Non-alcoholic Fatty Liver Disease/pathology
• Ultrasonography/methods

• cell death
• inflammation
• lipotoxicity
• nonalcoholic fatty liver disease

The dried mature fruit of Amomum villosum has been historically used in China as food and in the auxiliary treatment of digestive system disorders. Numerous studies have shown that gastrointestinal function is closely related to the development of nonalcoholic fatty liver disease via the “gut-liver” axis.

The present study aimed to explore whether the mechanism underlying the regulation of lipid accumulation in nonalcoholic fatty liver disease (NAFLD) may affect related disorders using the active ingredients in A. villosum.

Male Sprague-Dawley rats on a high-fat diet (HFD) to induce NAFLD were administered water extract of A. villosum (WEAV), volatile oil of A. villosum (VOAV), or bornyl acetate. After treatment, serum and liver total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured. The regulatory role of A. villosum in the microecology of the intestines was assessed using the V4 region of the 16S rDNA sequencing. The expression of the intestinal tight junction proteins occludin and ZO-1 was also measured. The influence of A. villosum on TLR4-mediated chronic low-grade inflammation was evaluated based on the concentrations of key proteins of the TLR4/NF-кB signaling pathway. Results. A. villosum effectively inhibited endogenous lipid synthesis, reduced TG, TC, and FFA accumulation, regulated the expression of LDL-C, and decreased lipid accumulation in liver tissues. VOAV effectively regulated the intestinal microflora, improved chronic low-grade inflammation by promoting ZO-1 and occludin protein expressions, and inhibited the TLR4/NF-кB signaling pathway.

The present study provides scientific basis for the potential application of A. villosum in NAFLD prevention and treatment. Additional chemical constituents other than bornyl acetate also contributed to the preventive effects of A. villosum on NAFLD.

• Anticoagulation
• Cirrhosis
• Fibrosis
• Heparin
• Inflammation
• Thrombosis

• Animals
• Blood Glucose/analysis
• Blood Pressure/physiology
• Catalase/analysis
• Catalase/genetics
• Catalase/metabolism
• Cholesterol/blood
• Diet, High-Fat
• Glycation End Products, Advanced/analysis
• Interleukin-1beta/blood
• Leukocytes/cytology
• Leukocytes/metabolism
• Liver/blood supply
• Liver/diagnostic imaging
• Liver/metabolism
• Male
• Microcirculation/physiology
• Non-alcoholic Fatty Liver Disease/metabolism
• Non-alcoholic Fatty Liver Disease/pathology
• Oxidative Stress
• Rats
• Rats, Wistar
• Real-Time Polymerase Chain Reaction
• Receptor for Advanced Glycation End Products/genetics
• Receptor for Advanced Glycation End Products/metabolism
• Triglycerides/blood
• Tumor Necrosis Factor-alpha/blood

• Conselho Nacional de Desenvolvimento Científico e Tecnológico
• PAPES/Fiocruz

• Cholecystectomy
• Elective procedure
• Fatty liver
• Gastric bypass
• Idiopathic noncirrhotic portal hypertension (INCPH)
• Liver biopsy

AIM: To identify the hepatic vascular architecture of patients with hepatitis C virus (HCV) using superb microvascular imaging (SMI) and investigate the use of SMI in the evaluation of liver fibrosis.

METHODS: SMI was performed in 100 HCV patients. SMI images were classified into five types according to the vascular pattern, and these patterns were compared with the fibrosis stage. Moreover, the images were analyzed to examine vascularity by integrating the number of SMI signals in the region of interest ROI [number of vascular trees (VT)]. The number of VT, fibrosis stage, serum parameters of liver function, and CD34 expression were investigated.

RESULTS: There was a significant difference between SMI distribution pattern and fibrosis stage (P < 0.001). The mean VT values in each of the fibrosis stages were as follows: 26.69 ± 7.08 in F0, 27.72 ± 9.32 in F1, 36.74 ± 9.23 in F2, 37.36 ± 5.32 in F3, and 58.14 ± 14.08 in F4. The VT showed excellent diagnostic ability for F4 [area under the receiver operator characteristic (AUROC): 0.911]. The VT was significantly correlated with the CD34 labeling index (r = 0.617, P < 0.0001).

CONCLUSION: SMI permitted the detailed delineation of the vascular architecture in chronic liver disease. SMI appears to be a reliable tool for noninvasively detecting significant fibrosis or cirrhosis in HCV patients.

• Superb microvascular imaging
• Number of vascular trees
• Chronic liver disease
• Ultrasound
• Liver fibrosis
• CD34

• Adult
• Aged
• Aged, 80 and over
• Antigens, CD34/metabolism
• Biopsy
• Cohort Studies
• Female
• Hepatitis C, Chronic/diagnostic imaging
• Hepatitis C, Chronic/metabolism
• Hepatitis C, Chronic/pathology
• Humans
• Immunohistochemistry
• Liver/blood supply
• Liver/diagnostic imaging
• Liver/metabolism
• Liver/pathology
• Liver Cirrhosis/diagnostic imaging
• Liver Cirrhosis/metabolism
• Liver Cirrhosis/pathology
• Male
• Microvessels/diagnostic imaging
• Middle Aged
• Neovascularization, Pathologic/diagnostic imaging
• Neovascularization, Pathologic/metabolism
• Neovascularization, Pathologic/pathology
• ROC Curve
• Retrospective Studies
• Ultrasonography

Non-Alcoholic Fatty Liver Disease (NAFLD) is now the most prevalent form of chronic liver disease, affecting 10%–20% of the general paediatric population. Within the next 10 years it is expected to become the leading cause of liver pathology, liver failure and indication for liver transplantation in childhood and adolescence in the Western world. While our understanding of the pathophysiological mechanisms underlying this disease remains limited, it is thought to be the hepatic manifestation of more widespread metabolic dysfunction and is strongly associated with a number of metabolic risk factors, including insulin resistance, dyslipidaemia, cardiovascular disease and, most significantly, obesity. Despite this, ”paediatric” NAFLD remains under-studied, under-recognised and, potentially, undermanaged. This article will explore and evaluate our current understanding of NAFLD in childhood and adolescence and how it differs from adult NAFLD, in terms of its epidemiology, pathophysiology, natural history, diagnosis and clinical management. Given the current absence of definitive radiological and histopathological diagnostic tests, maintenance of a high clinical suspicion by all members of the multidisciplinary team in primary and specialist care settings remains the most potent of diagnostic tools, enabling early diagnosis and appropriate therapeutic intervention.

• NAFLD
• adolescent
• children
• obesity
• steatosis

Hepatitis C virus (HCV) infection is associated with increased thrombotic risk. Several mechanisms are involved including direct endothelial damage by the HCV virus, with activation of tissue factor, altered fibrinolysis and increased platelet aggregation and activation. In advanced stages, chronic HCV infection may evolve to liver cirrhosis, a condition in which alterations in the portal microcirculation may also ultimately lead to thrombin activation, platelet aggregation, and clot formation. Therefore in advanced HCV liver disease there is an increased prevalence of thrombotic phenomena in portal vein radicles. Increased thrombin formation may activate hepatic stellate cells and promote liver fibrosis. In addition, ischemic changes derived from vascular occlusion by microthrombi favor the so called parenchymal extinction, a process that promotes collapse of hepatocytes and the formation of gross fibrous tracts. These reasons may explain why advanced HCV infection may evolve more rapidly to end-stage liver disease than other forms of cirrhosis.

• Coagulation
• Liver cirrhosis
• Hepatitis C virus
• Fibrogenesis
• Parenchymal extinction
• Portal thrombosis
• Protein C

• Animals
• Blood Coagulation
• Blood Platelets/metabolism
• Disease Progression
• End Stage Liver Disease/blood
• End Stage Liver Disease/virology
• Hepacivirus/pathogenicity
• Hepatic Stellate Cells/metabolism
• Hepatic Stellate Cells/pathology
• Hepatic Stellate Cells/virology
• Hepatitis C, Chronic/blood
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/diagnosis
• Hepatitis C, Chronic/therapy
• Hepatocytes/metabolism
• Hepatocytes/pathology
• Hepatocytes/virology
• Humans
• Liver/metabolism
• Liver/pathology
• Liver/virology
• Liver Cirrhosis/blood
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/therapy
• Liver Cirrhosis/virology
• Platelet Aggregation
• Portal Vein
• Risk Factors
• Thrombin/metabolism
• Venous Thrombosis/blood
• Venous Thrombosis/diagnosis
• Venous Thrombosis/therapy
• Venous Thrombosis/virology

• citral
• ginger essential oil
• lipogenesis
• nonalcoholic fatty liver disease
• obesity

• Acetyl-CoA Carboxylase/genetics
• Acetyl-CoA Carboxylase/metabolism
• Animals
• Diet, High-Fat/adverse effects
• Zingiber officinale/chemistry
• Humans
• Lipid Metabolism/drug effects
• Liver/drug effects
• Liver/enzymology
• Liver/injuries
• Liver/metabolism
• Male
• Mice
• Mice, Inbred C57BL
• Non-alcoholic Fatty Liver Disease/drug therapy
• Non-alcoholic Fatty Liver Disease/enzymology
• Non-alcoholic Fatty Liver Disease/genetics
• Non-alcoholic Fatty Liver Disease/metabolism
• Oils, Volatile/administration & dosage
• Oxidative Stress/drug effects
• Plant Extracts/administration & dosage
• Sterol Regulatory Element Binding Protein 1/genetics
• Sterol Regulatory Element Binding Protein 1/metabolism

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease and its incidence is increasing worldwide. However, the underlying mechanisms leading to the development of NAFLD are still not fully understood. Glycosyltransferases (GTs) are a diverse class of enzymes involved in catalyzing the transfer of one or multiple sugar residues to a wide range of acceptor molecules. GTs mediate a wide range of functions from structure and storage to signaling, and play a key role in many fundamental biological processes. Therefore, it is anticipated that GTs have a role in the pathogenesis of NAFLD. In this article, we present an overview of the basic information on NAFLD, particularly GTs and glycosylation modification of certain molecules and their association with NAFLD pathogenesis. In addition, the effects and mechanisms of some GTs in the development of NAFLD are summarized.

• Non-alcoholic fatty liver disease
• Pathogenesis
• Glycosyltransferases
• Glycosylation

• Adipose Tissue/enzymology
• Adipose Tissue/pathology
• Animals
• Glycosylation
• Glycosyltransferases/metabolism
• Humans
• Liver/enzymology
• Liver/pathology
• Non-alcoholic Fatty Liver Disease/enzymology
• Non-alcoholic Fatty Liver Disease/pathology
• Protein Processing, Post-Translational
• Signal Transduction

AGEs are a heterogeneous group of molecules formed from the nonenzymatic reaction of reducing sugars with free amino groups of proteins, lipids, and/or nucleic acids. AGEs have been shown to play a role in various conditions including cardiovascular disease and diabetes. In this study, we hypothesized that AGEs play a role in the “multiple hit hypothesis” of nonalcoholic fatty liver disease (NAFLD) and contribute to the pathogenesis of hepatosteatosis. We measured the effects of various mouse chows containing high or low AGE in the presence of high or low fat content on mouse weight and epididymal fat pads. We also measured the effects of these chows on the inflammatory response by measuring cytokine levels and myeloperoxidase activity levels on liver supernatants. We observed significant differences in weight gain and epididymal fat pad weights in the high AGE-high fat (HAGE-HF) versus the other groups. Leptin, TNF-α, IL-6, and myeloperoxidase (MPO) levels were significantly higher in the HAGE-HF group. We conclude that a diet containing high AGEs in the presence of high fat induces weight gain and hepatosteatosis in CD-1 mice. This may represent a model to study the role of AGEs in the pathogenesis of hepatosteatosis and steatohepatitis.

• Ecklonia cava
• MRI
• MRS
• NAFLD
• fatty liver
• hepatic steatosis

• Animals
• Cholesterol 7-alpha-Hydroxylase/genetics
• Cytokines/genetics
• Diet, High-Fat
• Disease Models, Animal
• Gene Expression Regulation/drug effects
• Inflammation/drug therapy
• Inflammation/pathology
• Lipid Metabolism/drug effects
• Lipogenesis/drug effects
• Lipogenesis/genetics
• Liver/drug effects
• Liver/pathology
• Male
• Mice
• Mice, Inbred C57BL
• Non-alcoholic Fatty Liver Disease/drug therapy
• Obesity/metabolism
• Phaeophyceae/chemistry
• Polyphenols/isolation & purification
• Polyphenols/pharmacology
• RNA, Messenger/metabolism

Objectives. To assess zinc (Zn) and vitamin D (Vit. D) status in chronic Hepatitis C virus- (HCV) infected patients and their relationship to interleukin- (IL-) 17 and disease severity and then investigate whether Zn and Vit. D3 modulate IL-17 expression in chronic HCV patients. Methods. Seventy patients and fifty healthy subjects were investigated. Serum levels of Zn, Vit. D, and IL-17 were assessed in the patients group and subgroups. Patients lymphocytes were activated in vitro in the presence or absence of Zn or Vit. D3 and then intracellular IL-17 production was assessed using flow cytometry. Results. Zn and Vit. D were significantly decreased in HCV patients. Increasing disease severity leads to more reduction in Zn level opposed by increasing IL-17 level. Zn potently reduced IL-17 production in a dose-related fashion; however it did not exert any toxic effects. Although Vit. D apparently increases IL17 expression, it is unclear whether it is due to its toxic effect on cell count or lack of definite association between Vit. D and both IL-17 and disease severity. Conclusions. This study demonstrates that Zn modulates IL-17 expression and provides a rationale for evaluating this compound as a supplementary agent in the treatment of chronic HCV.

Hepatic vena cava syndrome (HVCS) also known as membranous obstruction of inferior vena cava reported mainly from Asia and Africa is an important cause of hepatic venous outflow obstruction (HVOO) that is complicated by high incidence of liver cirrhosis (LC) and moderate to high incidence of hepatocellular carcinoma (HCC). In the past the disease was considered congenital and was included under Budd-Chiari syndrome (BCS). HVCS is a chronic disease common in developing countries, the onset of which is related to poor hygienic living condition. The initial lesion in the disease is a bacterial infection induced localized thrombophlebitis in hepatic portion of inferior vena cava at the site where hepatic veins open which on resolution transforms into stenosis, membrane or thick obstruction, and is followed by development of cavo-caval collateral anastomosis. The disease is characterized by long asymptomatic period and recurrent acute exacerbations (AE) precipitated by clinical or subclinical bacterial infection. AE is managed with prolonged oral antibiotic. Development of LC and HCC in HVCS is related to the severity and frequency of AEs and not to the duration of the disease or the type or severity of the caval obstruction. HVOO that develops during severe acute stage or AE is a pre-cirrhotic condition. Primary BCS on the other hand is a rare disease related to prothrombotic disorders reported mainly among Caucasians that clinically manifest as acute, subacute disease or as fulminant hepatic failure; and is managed with life-long anticoagulation, porto-systemic shunt/endovascular angioplasty and stent or liver transplantation. As epidemiology, etiology and natural history of HVCS are different from classical BCS, it is here, recognized as a separate disease entity, a third primary cause of HVOO after sinusoidal obstruction syndrome and BCS. Understanding of the natural history has made early diagnosis of HVCS possible. This paper describes epidemiology, natural history and diagnosis of HVCS and discusses the pathogenesis of LC in the disease and mentions distinctive clinical features of HVCS related LC.

• Hepatic venous outflow obstruction
• Budd-Chiari syndrome
• Hepatic inferior vena cava disease
• Bacterial infection
• Hepatocellular carcinoma

• Dissociation
• Insulin resistance
• Natural history
• Pathogenesis

• Cross-Sectional Studies
• Diabetes Mellitus, Type 2/epidemiology
• Humans
• Liver/physiopathology
• Longitudinal Studies
• Metabolic Syndrome/epidemiology
• Non-alcoholic Fatty Liver Disease/epidemiology
• Risk Factors

• cytokeratin-18
• enhanced liver fibrosis score
• fatty liver disease
• non-invasive hepatic biomarkers
• type 2 diabetes mellitus

• Aged
• Biomarkers/blood
• Cohort Studies
• Diabetes Mellitus, Type 2/complications
• Diabetes Mellitus, Type 2/epidemiology
• Fatty Liver/blood
• Fatty Liver/diagnosis
• Fatty Liver/epidemiology
• Fatty Liver/etiology
• Humans
• Keratin-18/blood
• Liver Cirrhosis/pathology
• Middle Aged
• Risk Factors
• Scotland/epidemiology

• CZB/4/582 Chief Scientist Office
• CZG/2/478 Chief Scientist Office
• G0500877 Medical Research Council
• G84/6205 Medical Research Council