BACKGROUND: Obesity is a global health problem that is associated with wide range of diseases, including atherosclerosis and Nonalcoholic fatty liver (NAFL) disease. Hepatic inflammation can cause cirrhosis, hepatic decompensation (liver failure) and cancer. Recent research now looks at the chronic systemic effects and inter-organ communication between atherosclerosis potentially promoting the development of NAFL. The resolution of inflammation is regulated naturally in the body by specialized pro-resolving mediators (SPMs). Immunoresolvents like ⍹6-derived Lipoxin A4 are suggested as a therapeutic strategy to overcome chronic inflammation and disease. In this study we investigated the therapeutic potential of Lipoxin A4 (LXA4) in cholesterol fed rabbit model of hypercholesterolemia, with atherosclerotic plaques and confined vascular endothelial injury and its effect on the progression of NAFL. OBJECTIVE: This is a continuation of studies pioneered in the Hamilton lab and an extension of the recent study by Taylor et. al in 201811 linking aortic plaque and liver disease. We will now investigate the therapeutic potential of Lipoxin A4 on lipid-rich atherosclerotic plaques in cholesterol fed rabbits and its effect on the progression of NAFL to NASH. METHODS: In vivo magnetic resonance imaging (MRI) measured aortic atherosclerotic inflammation (with plaque Gd-enhancement), plaque size (vessel wall area), and composition, within rabbits fed normal chow or a 1% cholesterol-enriched diet. Biomarkers in the blood were monitored in the rabbits, with follow-up by histology, which included Masson’s trichrome staining. Light Microscopy was used for liver imaging. Ex vivo MRI, T1W imaging was used to quantify VWA (vessel wall area), with Image J programming. RESULTS: Cholesterol-fed rabbits with and without aortic injury developed hypercholesterolemia, NAFL, and atherosclerotic plaques in the aorta. Elevated plasma gamma-glutamyl transferase (GGT; p =0.014) and the ratio of liver enzymes aspartate and alanine aminotransferases (AST/ALT; p = 0.033) confirmed the progression of steatosis to non-alcoholic steatohepatitis (NASH). Histological images showed less fibrosis in those rabbits fed 1% CHOL diet with injury treated with LipoxinA4, when compared to 1% CHOL diet and injury alone. The plasma biomarkers showed a decrease in cholesterol (79%) and triglycerides (49.9%) in those rabbits given LXA4 therapy. The LXA4 treated 1% CHOL diet with injury group showed a marked decrease in the aorta vessel wall area when compared to the 1% CHOL diet with injury, without treatment; as seen in ex vivo, MRI T1W imaging. CONCLUSION: Lipoxin implementation in cholesterol fed rabbits that have localized regions of highly inflamed aortic atherosclerotic plaques, may contribute to the attenuation on the progression of NAFL to NASH as seen in histology and plasma biomarkers including; cholesterol and triglycerides. Lipoxin as a therapeutic has an effect on treating atherosclerotic plaques and attenuating atherosclerosis progression.

The overall clinical motivation of this thesis is to differentiate between the different stages of liver disease stratifying into: no disease, mild disease, and severe fibrosis using Magnetic Resonance Imaging (MRI). As a related aim, we seek to differentiate as much as possible pericellular and nonpericellular fibrosis. This latter is clinically important, but currently no method exists that is able to perform this. Quickly, we realised that these aims push low level image analysis beyond their current bounds and so a great deal of the thesis is dedicated to extending such techniques before they can be applied. To work on the most fundamental low level image analysis concepts and algorithms we choose one of the most recent developments, namely continuous intrinsic dimensionality (ciD), which allows the continuous classification of homogeneous patches from 1D structures to intrinsically 2D structures. We show that the current formalism has several fundamental limitations and we propose a number of developments to improve on these. We re-evaluated feature energy statistics that were originally proposed in ciD, and additionally we examined the confidence one may have in stateof- the-art methods to estimate the orientation of features. We show that new statistical methods are required for feature energy, and that orientation predictability is more important than correctness of the estimation. This evaluation led us to the monogenic signal local orientation. Analysis of feature or texture energy is also a main contribution of this thesis. Within this framework we propose the Riesz-weighted phase congruency model. This is able to detect internal texture structures but it is not capable of delineating boundaries. Nevertheless, it proves an appropriate basis for texture quantification. Finally, we show that in contrast to using the standard established Kovesi approach, the developed texture measure leads to good results on the suboptimal T1w MRI liver image staging images. We show that we are able to differentiate automatically between the separate disease scores and between pericellular and non-pericellular fibrosis.

Background: Liver is a vital organ that plays a major role in glucose production and regulationthroughout the body (Musso et al., 2012). Liver disease has long been linked with insulin resistance (IR), dating back to 1906 (Megyesi et al., 1967). IR has been found to be prevalent in a range of liver diseases, including chronic Hepatitis C Virus (HCV), hemochromatosis, and alcoholic liver disease (Goswami et al., 2014). Liver disease is highly prevalent in the United States population with 30 million people (or one out of ten Americans) suffering from some type of liver disease (Peery et al., 2015). Although research demonstrates a significant relationship between liver disease and IR, the University of Arizona (UA) hepatology clinic does not currently screen liver disease patients for IR. Homeostatic model assessment for insulin resistance (HOMA-IR) score is used to study IR in non-insulin resistant population. HOMA-IR score is calculated using formula fasting plasma glucose (mmol/l) times fasting serum insulin (mU/l) divided by 22.5 (Bonora et al., 2002). Low HOMA-IR (HOMA< 2.0) values indicate high insulin sensitivity, whereas high HOMA-IR (HOMA> 2.0) values indicate low insulin sensitivity (insulin resistance) (Bonora et al., 2002). Objective: The purpose of this quality improvement (QI) project is to show the prevalence of IR in euglycemic liver disease patients at the UA hepatology clinic by using their HOMA-IR scores as a screening tool. By screening euglycemic liver disease patients for IR based on their HOMA-IR score, providers at the UA hepatology clinic can prevent liver disease progression and complications associated with IR early on. By doing so, the providers can improve the quality of care for liver disease patients. An essential part of calculating HOMA-IR is the availability of labs (serum glucose and serum insulin). A part of this QI project is to determine if the UA hepatology clinic has necessary labs to calculate HOMA-IR for euglycemic liver disease patients. A related matter is whether there is a correlation between liver disease patients' HOMA-IR score and Model for End-stage Liver Disease (MELD) score. If there is a direct correlation between HOMA-IR and MELD scores, providers can identify severity and progression of liver disease in euglycemic liver disease patients. Design: A case control retrospective study. Study Questions: 1) Do UA Hepatology clinic providers order sufficient labs (fasting plasma glucose and fasting plasma insulin) to calculate HOMA-IR in euglycemic patients? 2) What is the prevalence of IR in euglycemic liver patients indicated by HOMA-IR score? 3) Is there any correlation between HOMA-IR score and MELD score in euglycemic liver disease patients? Participants: Data will be collected from 1000 liver disease patients' at the UA hepatologyclinic, a tertiary level referral center. Settings: Banner University Medical Center (UMC) in Tucson, Arizona from January 1, 2011 until December 31, 2014. Measurements: HOMA-IR score using serum fasting glucose and serum fasting insulin levels laboratory values. MELD score to identify the severity of liver disease in euglycemic liver disease patients. Results: Among 1000 patients, 506 (60.5%) were found to have a previous diagnosis of T2DMand 395 (39.5 %) were euglycemic liver disease patients (Figure 1). Out of the 395 euglycemic liver disease patients, 217 (55%) participants were found to have both insulin level and glucose11level in their charts; 178 (45%) euglycemic liver disease patients were missing either insulin level or glucose level needed to calculate HOMA-IR score (Figure 2). Of the 217 euglycemic liver disease patients, 54.8% of had HOMA-IR> 2 and 45.2% patients had HOMA-IR<2 (Figure 3). The Pearson Correlation between HOMA-R>2 and MELD scores was 0.092 and the significance value using 2-tailed was 0.321 (Table 4). Conclusion: The results showed a significant high prevalence of IR in euglycemic patients with HOMA-IR score> 2 (54.8%) compare to those patients with HOMA-IR score<2 (45.2%). Furthermore, about 178 (45%) euglycemic liver disease patients were missing either insulin level or glucose level needed to calculate HOMA-IR score. This is a significant number of patients missing important labs to identify them as high risk for IR. This QI project identified HOMA-IRas an important screening tool that should be used both in hepatology clinics and primary healthcare settings. Use of such tool will lead to improved quality of care for euglycemic liver disease patients.

A dosagem de gama-glutamil transpeptidase sérica (GGT) tem sido amplamente utilizada como marcador bioquímico do uso de álcool. Sua utilização no rastreamento do consumo de álcool em pacientes com doença hepática diagnosticada necessita ser melhor investigada. Neste estudo foram comparados os níveis séricos de GGT ao padrão de consumo de álcool avaliado por meio do teste de rastreamento AUDIT em 126 indivíduos hepatopatas (94 homens e 32 mulheres), com idade entre 20 a 69 anos. Vinte e dois indivíduos (17,4%) obtiveram pontuação maior ou igual a 8 no AUDIT (casos positivos para suspeição de problemas relacionados ao consumo de álcool nos últimos 12 meses). Este percentual eleva-se a 32,7% nos pacientes com diagnóstico de hepatopatia associada ao uso do álcool. A gravidade da hepatopatia foi avaliada com base na classificação de Child-Pugh: 86 pacientes foram classificados como A (68,2%) e 40 como B ou C (31,8%). Todos os pacientes com pontuação &#8805;8 no AUDIT foram do sexo masculino e 77,3% deles tiveram diagnóstico de doença hepática associada ao uso de álcool (p<0,0001). Pacientes com pontuação &#8805;8 no AUDIT apresentaram valores médios de GGT significantemente maiores quando comparados àqueles menores que 8 (526,9 U/L ± 1006,8 versus 138,7 U/L ± 123, p<0,00001). O teste de correlação de Pearson indicou uma forte associação entre a elevação dos valores de GGT em pacientes hepatopatas que fazem uso de álcool e a pontuação total no AUDIT. Pacientes hepatopatas, apesar de manifestarem valores elevados de GGT, as diferenças não estiveram relacionadas à gravidade da hepatopatia. Não houve diferença estatisticamente significante em relação à pontuação &#8805;8 no AUDIT e idade, estado civil, situação de emprego, escolaridade, renda familiar, cor e religião. Nossos dados sugerem que a utilização combinada do GGT e do AUDIT pode ser útil em discriminar pacientes hepatopatas usuários de álcool, principalmente em países em desenvolvimento como o Brasil, devido ampla disponibilidade e baixo custo. / The gamma glutamyltranspeptidase (GGT) has been widely employed as excessive alcohol use biochemical marker. Its utilization in screening of alcohol consumption in patients with diagnosed liver diseases must be better investigated. In this study, serum levels of GGT were compared to the pattern of alcohol consumption using the AUDIT test as alcohol screening instrument in 126 patients with liver disease (94 men and 32 women), with age ranged from 20 to 69 years old. Twenty two patients (17,4%) scored higher or equal 8 in the AUDIT (positive cases for alcohol related problems suspicion in the last 12 months). This proportion increases to 32,7% in patients with alcohol-associated liver disease. The severity of the liver damage was evaluated by the Child-Pugh classification: 86 patients were classified as A (68,2%) and 40 as B or C (31,8%). All patients who scored 8 or higher in the AUDIT were men and had mean values of GGT significantly higher when compared to those who scored less than 8 (526,9 U/L ± 1006,8 versus 138,7 U/L ± 123, p<0,00001). Among them 77,3% had alcohol-associated liver disease diagnosis (p<0,0001). The Pearson’s correlation test showed a strong association between increase of the GGT values in patients that use alcohol and total score in the AUDIT. No association between increase of GGT values and severity of liver damage was found. No statistically significance was observed also between AUDIT scores 8 or higher to age, civil status, employment situation, education, familiar earnings, race or religion. Our data suggest that the combined use of GGT and AUDIT can be useful in discriminating liver disease patients that use alcohol, particularly in developing countries like Brazil, due to their widely availability and low costs.

Nonalcoholic fatty liver disease (NAFLD) afflicts approximately a quarter of the world’s general population and more than half of the world’s obese population. The disease is characterized by a spectrum of liver pathologies, ranging from simple steatosis or the accumulation of fat within hepatic tissue to steatohepatitis comprised of inflammation and fibrosis, also known as NASH. Simple steatosis is relatively asymptomatic and is considered benign, but NASH poses great risk for advanced forms of liver disease, such as cirrhosis and hepatocellular cancer. Obstructive sleep apnea(OSA) is a respiratory disorder involving the recurrent collapse of the upper airway during sleep. Consequently, the patient experiences constant arousals due to constant blockage followed reopening of the airway. Aside from poor quality and disruption of sleep, chronic intermittent hypoxia (CIH) is also present during OSA. The presence of CIH leaves many vital organs deprived of adequate oxygen to carry out normal physiological function. In response to this hypoxic state, the body upregulates many transcription factors, many of which control inflammatory processes. In recent studies, chronic and recurrent hypoxia generated from OSA has been implicated in the onset and progression of NAFLD. The pathogenesis of NAFLD is believed to be associated with metabolic imbalances, mainly obesity and insulin resistance, both of which also overlap with OSA. These conditions are the main factors in predisposing a patient suffering from OSA to the effects of CIH. Multiple lines of evidence suggest that CIH may accelerate the development of NAFLD through 1) Lipolysis of hepatic adipose tissue and increased hepatic free fatty acids; 2) Upregulation of lipid biosynthetic through CIH; 3) Upregulation of hypoxia-inducible factor 1-alpha by CIH inducing liver inflammation and fibrosis. The primary focus of this thesis will attempt to determine a possible link between OSA and NAFLD. Through citation of prior scientific studies, it will formulate the theory of OSA as a predisposing factor in the heightened risk of NAFLD pathogenesis and development to more severe, terminal stages. Primarily, the review of literature will highlight the metabolic imbalances of obesity and insulin resistance and how each is related to OSA and NAFLD. Ultimately, deposition of fat and inflammation triggered through various chemical factors connected to OSA will depict both the generation and progression of NAFLD.

Made available in DSpace on 2014-06-11T19:22:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-11-17Bitstream added on 2014-06-13T19:27:11Z : No. of bitstreams: 1 lucchesi_an_me_botfm.pdf: 749829 bytes, checksum: 0aa5e082ee905bd7a05a8698d3112ee3 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O diabetes mellitus (DM) é tido como um problema de saúde pública mundial. No Brasil ele atinge mais de 14 milhões de pessoas, sendo acompanhado de altos índices de morbidade e mortalidade. Entretanto, os mecanismos primariamente responsáveis pela agressão dos tecidos e órgãos pelo DM ainda não são completamente conhecidos, o que explica a dificuldade em se estabelecer um tratamento eficaz para prevenir ou controlar a progressão das lesões diabéticas crônicas. O estresse oxidativo celular é tido como um dos mecanismos importantes na gênese do dano tecidual relacionado à hiperglicemia. Através deste mecanismo, o DM poderia aumentar a produção de espécies reativas do oxigênio (EROs) ao nível celular, que pela sua toxicidade, seria capaz de promover o desenvolvimento das lesões diabéticas crônicas. Evidências clínicas sugerem que o fígado de indivíduos diabéticos também poderia sofrer a ação das EROs, no longo prazo, levando a uma seqüência de eventos capaz de determinar a doença gordurosa do fígado de etiologia não-alcoólica (DGFNA), com progressão para esteato-hepatite e cirrose. Todavia, a presença de estresse oxidativo no tecido hepático de portadores de DM, ainda não está bem estabelecida na literatura, o que justifica a realização de novas investigações em modelos-animais de diabetes, no intuito de melhor esclarecer a real participação deste mecanismo na gênese e evolução das lesões hepáticas diabéticas crônicas. Neste estudo foram utilizados 60 ratos machos Lewis, distribuídos em 2 grupos experimentais, com 30 animais cada um, assim designados: GN - Grupo Controle: constituído de ratos normais, não-diabéticos; GD - Grupo Diabético: constituído por animais diabéticos induzidos pela aloxana, sem qualquer tratamento. Cada um dos grupos experimentais foi dividido em 3 subgrupos de ratos, com 10 animais cada um, para serem... / Diabetes mellitus (DM) is considered to be a public-health problem worldwide. In Brazil, it affects 14 million people, and it is accompanied by high morbidity and mortality rates. However, the mechanisms primarily responsible for tissue and organ aggression by DM are not yet fully known, which explains the difficulty in establishing effective treatment to prevent or control the progression of chronic diabetic lesions. Cellular oxidative stress is considered to be one of the important mechanisms in the genesis of hyperglycemia-related tissue damage. Through this mechanism, DM could increase the production of reactive oxygen species (ROS) in the cellular level, which, due to their toxicity, could promote the development of chronic diabetic lesions. Clinical evidence suggests that the liver of diabetic individuals could also suffer the action of ROS in the long term, thus leading to a sequence of events that can determine non-alcoholic fatty liver disease (NAFLD), with progression to steatohepatitis and cirrhosis. However, the presence of oxidative stress in the hepatic tissue of individuals with DM has not been yet well established in the literature, which justifies the performance of new investigations in diabetes animal models with the purpose to clarify the actual participation of such mechanisms in the genesis and development of chronic diabetic hepatic lesions. In this study, 60 males Lewis rats were used. They were distributed into 2 experimental groups, each containing 30 animals and designated as follows: GN – Control Group: consisting of non-diabetic control rats; GD – Diabetic Group: consisting of alloxan-induced diabetic rats without any treatment. Each experimental group was divided into 3 subgroups of rats with 10 animals each to be evaluated and sacrificed respectively at 4 experimental moments, namely: M1– animals from the 3 subgroups, at the initial moment... (Complete abstract click electronic access below)

Non-alcoholic fatty liver disease (NAFLD) is a worldwide health problem which includes steatosis (triglyceride accumulation alone), non-alcoholic steatohepatitis (NASH, with liver inflammation), fibrosis, cirrhosis and hepatocellular carcinoma. Liver fibrosis, which is a reversible response, is the final phase of most chronic liver disease and is characterized by accumulation of extracellular matrix (ECM) from activated hepatic stellate cells (HSCs). Glucocorticoids (GCs) regulate many aspects of metabolism involved in NAFLD. Also, GCs limit HSC activation in vitro. Tissue GC levels are regulated by 11β- hydroxysteroid dehydrogenase-1 (11β-HSD1) which converts inactive 11- dehydrocorticosterone (DHC) into active corticosterone. Previous studies demonstrate that 11β-HSD1 deficiency improves fatty liver in obesity models, but the role of 11β-HSD1 in mechanisms involved in the progression and/or resolution of hepatic injury is largely unknown. I hypothesized that 11β-HSD1 modulates fibrotic and inflammatory responses during hepatic injury and/or the resolution phase. First I sought to address if the levels of 11β-HSD1 during different models of liver injury are dysregulated. In mice, 11β-HSD1 was down-regulated in choline deficient diet (CDD) induced steatosis, methionine and choline deficient diet (MCDD) induced NASH, carbon tetrachloride (CCL4) induced liver fibrosis and thioacetamide (TAA) induced liver fibrosis. In CCL4 injured livers, the down regulation of 11β- HSD1 was observed around the scar area. To test if 11β-HSD1 plays a key role in modulating liver inflammation and fibrosis responses in NAFLD and liver fibrosis I used initially11β-HSD1 knockout (KO) mice. 11β-HSD1 KO showed higher HSC activation only in the High fat feeding model but not in CDD and MCDD models. In the CCL4 injury model, despite reduced hepatocellular injury, 11β-HSD1 KO mice showed enhanced collagen deposition during peak injury and increased fibrotic gene expression during the early resolution phase although unaltered inflammatory markers during both peak injury and resolution. To further dissect cell-specificity on the effect of 11β-HSD1, I repeated the CCL4-injury model using the hepatocyte-specific 11β-HSD1 KO (Alb-HSD1). Alb-HSD1 mice did not show increased susceptibility to fibrosis compared to control littermates suggesting that the 11β- HSD1 possibly modulates fibrotic response by affecting HSC function. To mechanistically address how GCs inhibit HSC activation in vitro I studied the effects of 11β-HSD1 on HSC in vitro. 11β-HSD1 expression was down-regulated during ‘spontaneous’ HSC activation, and 11β-HSD1 deficiency enhanced susceptibility to activation. The GC (11-DHC)’s inhibitory effect on HSC activation was reversed by 11β-HSD1 inhibition. Finally, to address the clinical relevance of 11β-HSD1 in hepatic injury and/or resolution a selective 11β-HSD1 inhibitor, UE2316, was used. UE2316 induced a pro-fibrotic phenotype in ob/ob mice and CCL4-treated C57BL/6 mice, but had no effect when administered only during injury resolution. In conclusion, 11β-HSD1 deficiency causes increased activation of HSCs following diet and chemical injury and promotes liver fibrosis. Effects of 11β-HSD1 inhibitors, which are a potential treatment for metabolic syndrome, are perhaps offset by adverse outcomes in liver.

This thesis investigates the epidemiology of hepatitis B virus infection (HBV) and estimates HBV-related liver disease burden in Vietnam and Australia using a cross-sectional study design and mathematical modelling. A population-based seroprevalence survey was undertaken in rural Northern Vietnam. In a sample of 870 study participants, prevalence of anti-HBV core antibody (anti-HBc) and hepatitis B virus surface antigen (HBsAg) was 68.2% and 19.0%, respectively, and hepatitis B e antigen (HBeAg) was detected in 16.4% of the HBsAg-positive group. Factors associated with HBV infection (anti-HBc and/or HBsAg-positive) were age 60 years or older (adjusted odds ratio (AOR), 3.82; 95% CI, 1.35??10.80; P = 0.01), residence in Vu Thu district (AOR, 3.00; 95% CI, 2.16??4.17; P <0.001), hospital admission (AOR, 2.34; 95% CI, 1.33??4.13; P = 0.003) and history of acupuncture (AOR, 2.01; 95% CI, 1.29??3.13; P = 0.002). Household contact with a person with liver disease (AOR, 2.13; 95% CI, 1.29??3.52; P = 0.003), reuse of syringes (AOR, 1.81; 95% CI, 1.25??2.62; P = 0.002) and sharing of razors (AOR, 1.69; 95% CI, 1.03??2.79; P = 0.04) were independent predictors of HBsAg positivity. Alanine aminotransferase (ALT) level was elevated (>40 IU/L) in 43% of the HBsAg-positive group; the proportion of elevated ALT was higher in HBeAg-positive (65%) compared with HBeAg-negative (39%) (P = 0.02). Based on data from the seroprevalence study, other prevalence estimates and HBV natural history parameters, a mathematical model was used to estimate HBV-related liver disease burden in Vietnam. Estimated chronic HBV prevalence increased from 6.4 million cases in 1990 to around 8.4 million cases in 2005 and was projected to decrease to 8.0 million by 2025. Estimated HBV-related liver cirrhosis and hepatocellular carcinoma (HCC) incidence increased linearly from 21 900 and 9400 in 1990 to 58 650 and 25 000 in 2025. Estimated HBV-related mortality increased from 12 600 in 1990 to 40 000 in 2025. To estimate HBV-related HCC incidence among Australians born in the Asia-Pacific region (APR), a mathematical modelling was developed utilising HBV natural history parameters, HBV prevalence estimates in APR countries and immigration data. Chronic HBV cases among the APR-born population increased rapidly from the late 1970s, reaching a peak of 4182 in 1990. Chronic HBV prevalence increased to more than 53 000 in 2005. Estimates of HBV-related HCC increased linearly from one in 1960 to 140 in 2005, with a projected increase to 250 in 2025. Universal HBV vaccination programs in countries of origin had limited impact on projected HBV-related HCC to 2025. HBV-related HCC survival was analysed in a population-based linkage study in New South Wales (NSW), Australia. Between 1994 and 2002, 278 HCC cases notified to the NSW Cancer Registry were linked to chronic HBV infection notifications to the NSW Health Department. The majority of cases were male (83.5%) and overseas born (93.6%); Asian-born cases accounted for 72.1%. Median survival following HCC diagnosis was 15 months. HCC survival was poorer among older age groups (P <0.001), and among cases with regional spread (HR 3.23; 95% CI, 1.83??5.69; P <0.001) and distant metastases (HR 3.85; 95% CI, 2.44??6.08; P <0.001). Sex, region of birth, and study period (1994??1997 versus 1998??2002) were not associated with HCC survival. The results of these studies show that HBV infection remains a major public health challenge in highly endemic countries such as Vietnam. HBV-related liver disease burden in Vietnam was estimated to increase for at least two decades despite the introduction of a universal infant HBV-vaccination program. Similarly, HBV-related HCC among Australians born in the APR was estimated to continue to increase over the next two decades. Survival for HBV-related HCC even in settings such as Australia continues to be extremely poor. Strategies are required to expand HBV treatment to individuals with chronic HBV infection who are at greatest risk of progression to advanced liver disease.

To examine the relationship between liver injury and the appearance of bone marrow derived hepatic cells we performed sex-mismatched bone marrow transplants in mice, with subsequent liver injury. Co-labeling for a marker of donor bone marrow origin and a marker of liver epithelial phenotype allowed us to identify rare marrow-derived hepatocytes at various time points following liver damage. The number of marrow-derived hepatocytes was low, however, and did not allow us to determine if liver-specific injury upregulated this process from baseline. We conclude that while marrow-derived hepatocytes are found, the low level of occurrence in this study makes it impossible to draw a clear temporal relationship between liver damage, recovery and the appearance of donor-derived cells. In addition, we cannot say whether liver-specific damage upregulates this phenomenon.

No description available.