This month Dr Michael Charlton has offered his turn at the microp

This month Dr Michael Charlton has offered his turn at the microphone

to Dr. Donald Jensen and Dr Andrew Aronsohn from the University of Chicago, in order that they can address a pressing issue that will emerge in tandem with the likely approval by the U.S. Food and Drug Administration of boceprevir and/or telaprevir. DAA, direct-acting antiviral; HCV, hepatitis C virus. More than 120 million people are infected with hepatitis C worldwide.1 Hepatitis C virus (HCV) is a leading cause of liver-related mortality and is the most common indication for liver transplantation in the United States.2 Since the introduction of pegylated this website interferon and ribavirin nearly 10 years ago, response rates have been relatively stagnant, with less than half of treated patients achieving a sustained virological response.2 Data from the first direct-acting antiviral (DAA) agent, BILN 2061, was initially presented at the American Association for the Study of Liver Diseases annual meeting in 2002, which sparked enthusiasm over improving therapeutic efficacy.3

Nearly a decade later, we find ourselves on the brink of a new era of HCV therapy. Telaprevir Trametinib and boceprevir will likely receive U.S. Food and Drug Administration approval by mid-2011, and based on phase 2 and 3 data, will significantly improve rates of sustained virological response in patients infected with HCV genotype 1 when compared to current standard-of-care therapy.4-7 This improved efficacy has been well-publicized for years, and anticipation of DAA availability

has already become part of the HCV treatment algorithm. Greater understanding of the natural history of HCV and identification of risk factors for progression to advanced liver disease has allowed many physicians to recommend deferral of standard-of-care therapy in favor of waiting for DAA availability Etoposide research buy for patients who are at low risk to progress to significant liver disease in the near future. This was demonstrated in a large VA-based study of 4084 patients evaluated for HCV therapy with interferon and ribavirin.8 Of the eligible patients who declined therapy, 50.3% stated they had deferred treatment in anticipation of more effective medications.8 Treatment-naive patients who have deferred standard-of-care therapy, in addition to patients who have failed previous regimens of HCV treatment, will likely create a surge of requests to initiate therapy in mid-2011. The influx of patients requesting HCV therapy will present a significant problem. HCV therapy is becoming increasingly complex, and the addition of DAAs will only add to the time needed to effectively educate and appropriately monitor patients while they are receiving treatment. This may be partially offset by response-guided therapy that shortens treatment duration.

The aim of this study was to assess the prevalence of NAFLD in ol

The aim of this study was to assess the prevalence of NAFLD in older Australians and their self-awareness of this problem. Methods: We recently completed a comprehensive health survey of residents, over the age of 65, living on the Central Coast. We recruited 831 community-based participants who completed a questionnaire assessing their medical history, including 5-Fluoracil datasheet all types of liver diseases, metabolic risk factors, medications and alcohol

intake. These subjects had their BMI, body anthropometry and biochemistry analysed. Fatty liver index (FLI)2 is a validated non-invasive method of estimating the likelihood of NAFLD in individuals. FLIs were calculated and subjects classified into three categories, FLI < 30 (No NAFLD), 30 ≤ FLI < 60 (Borderline) and FLI ≥ 60 (NAFLD). Local Human Research Ethics Committee approval was given and informed consent obtained. Results: For analysis, subjects with other liver diseases and alcohol intake > 20 g/day

were excluded, leaving 510 individuals. Only one of the participants with FLI≥ 60 and one with a borderline value self-reported NAFLD. Results are given as means ±SD.   Fatty Liver Index p value <30 ≥60 n (%) 135 (26.5) 226 (44.3)   Age (yrs) 78.7 ± 7.5 77.1 ± 6.5 ns Sex (F/M) 100/35 111/115  < 0.0001 BMI (kg/m2) 23.4 ± 2.5 32.0 ± 4.1  < 0.0001 Waist circumference (cm) 83.4 ± 7.6 108.3 ± 9.8  < 0.0001 ALT (U/L) 20.3 ± 9.4 23.8 ± 11.2 0.011 γ-glutamyltransferase (U/L) 23.9 ± 11.3 44.5 ± 43.0 <0.0001 Triglycerides SCH727965 datasheet (mg/dL) 84.3 ± 31.3 149.7 ± 66.3 <0.0001 Type 2 DM (%) 7 (5.3) 51 (22.7) <0.0001 Insulin (mIU/L) 4.8 ± 3.1 10.9 ± 6.9 <0.0001 Alcohol intake (g/day) 4.6 ± 6.1 5.4 ± 6.2 ns Conclusions: This is the first report of the prevalence of NAFLD in an elderly

Australian population (44.3%) and this value is higher than clonidine the previous estimates used. Older Australians appear to be unaware of this condition and its impact on their health. 1 GESA/ALA. The economic cost and health burden of liver disease in Australia. Deloitte Access Economics, February 2013 2 Koehler E et al. External Validation of the Fatty Liver Index for Identifying Nonalcoholic Fatty Liver Disease in a Population-based Study. Clin Gastroenterol Hepatol. 2013 doi:10.1016/j.cgh.2012.12.031 E ZHAO,1 L HORSFALL,2 BJ RUFFIN,3 KJ FAGAN,1,2 KM IRVINE,1 EE POWELL1,2 1Centre for Liver Disease Research, School of Medicine, The University of Queensland, Translational Research Institute, Princess Alexandra Hospital; 2Department of Gastroenterology and Hepatology, Princess Alexandra Hospital; Brisbane, 3The University of Queensland, School of Nursing. Introduction: Ascites is the most common complication of cirrhosis, a chronic disease state that leads to recurrent hospital admissions and huge health-care costs. In other common chronic diseases such as congestive heart failure and chronic obstructive pulmonary disease, risk factors for early readmission have been identified.

1997) Finally, there is no indication of infection or related pa

1997). Finally, there is no indication of infection or related pathologies from surgical biopsy wounds (Weller et al. 1997). Bruce-Allen and Geraci (1985) described

the wound healing process in captive bottlenose dolphins following incisions through the epidermis and into the dermis. Their study demonstrated that cuts are histologically repaired by 7 Lorlatinib order d, but are still visible on dolphins as white linear marks. High rates of cell proliferation enable cetaceans to rapidly heal from wounds they obtain in their natural habitat. For example, bottlenose dolphins with large, open wounds, probably inflicted by sharks, heal substantially within the first month and can be completely healed within 6–7 mo (Corkeron et al. 1987, Lockyer and Morris 1990). The successful healing of these larger traumas in the wild is perhaps one of the strongest arguments to suggest

that the majority of biopsy wounds will heal rapidly and that biopsy sampling will most likely not impact survival (International Whaling Commission 1991). Aguilar and Borrell (1994a) also concluded that the small wound produced by a standard biopsy dart (0.25 cm diameter) should not lead to significant physical trauma in sampled animals. To date, no studies have investigated the stress response in cetaceans targeted by remote biopsy sampling methods. In comparison, a small number of researchers have investigated physiological and behavioral responses in dolphins to assess selleck products stress associated with encirclement by nets and handling, which are required during manual biopsy procedures. St. Aubin et al. (1996) found that bottlenose dolphins had elevated stress hormones (aldosterone and cortisol) following capture and handling, check details while most dolphins in a similar study by Ortiz and Worthy (2000) did not exhibit elevated stress hormone levels. Authors of both studies concluded that the increases in hormone levels were indicative of a mild stress response

only. Another study found that bottlenose dolphin blood cells increase gene expression related to metabolism and stress, which also indicates that dolphins undergo a stress response during capture-release health assessments (Mancia et al. 2008). Finally, Esch and colleagues (2009) showed that signature whistle parameters, which may be potential indicators of stress, changed in bottlenose dolphins during brief capture-release events. However, none of the studies examined the long-term impacts of these short-lived stress responses or how physiological responses change with repeated captures of the same individual. These, as well as examining the stress response in remotely biopsied cetaceans, are important areas of future research, as the cumulative impacts of repeated capture and/or biopsy sampling (by both manual and remote methods) may be substantial.

The Paris criteria were recognized as the best validated and easi

The Paris criteria were recognized as the best validated and easiest to use.7, 11 Using published criteria, we sought selleck compound to determine whether a biochemical response as early as 3 to 6 months instead of 1 year would similarly identify patients with poor long-term outcome; if true, it could facilitate a more rapid selection of patients suitable

for new therapeutic approaches. In the present study, we analyzed prospectively collected data of 187 patients with a mean follow-up period of 5.9 years. First, we found that serum bilirubin, ALP, GGT, AST, ALT, and IgM levels most prominently decreased within the first 3 months of UDCA therapy. These laboratory parameters continued to decrease gradually, with the maximum response seen at either 6 months or 1 year. Second, we found that the Paris, Barcelona, Toronto, and Ehime definition applied at 3, 6, and 12 months all significantly Selleckchem Stem Cell Compound Library discriminated the patients

in terms of long-term outcome, whereas no significant association was found with the Rotterdam definition (Table 3 and Fig. 3). Finally, we found that biochemical response at the sixth month can more accurately identify patients with good or poor prognosis compared with that at 1 year. The long-term evolution of laboratory liver parameters beyond 1 year UDCA therapy has been documented, suggesting that biochemical response to UDCA can be maintained for up to 15 years.3, 16 In contrast, laboratory parameters within the first year were seldom reported in a large cohort of patients. Our cohort consisted of 187 patients who were followed at 3-month

intervals. Laboratory investigations were performed and data were collected prospectively. All of the laboratory parameters studied showed a prominent improvement in the first 3 months and then stayed relatively stable for the following months within the first C1GALT1 year of UDCA treatment (Fig. 1). This led us to hypothesize that an early biochemical response as short as 3 to 6 months may be used in place of that after 1 year of UDCA therapy. We then evaluated the prognostic impact of multiple criteria in our patients. By all definitions except the Rotterdam criteria, biochemical response at 3, 6, and 12 months significantly discriminated our patients in terms of long-term outcome (Table 3 and Fig. 3). Our results tend to agree with those of the study recently published by the Paris group.14 The Paris group’s study included 165 patients with early PBC, and no significant association was found between the long-term outcomes and the Rotterdam definition. Since the Rotterdam criteria have been demonstrated to be more potent prognostic indicators of long-term outcome in late rather than early stages of PBC,8 they may not be applicable in a cohort of patients that contains high proportions of early PBC.

The Paris criteria were recognized as the best validated and easi

The Paris criteria were recognized as the best validated and easiest to use.7, 11 Using published criteria, we sought Rapamycin to determine whether a biochemical response as early as 3 to 6 months instead of 1 year would similarly identify patients with poor long-term outcome; if true, it could facilitate a more rapid selection of patients suitable

for new therapeutic approaches. In the present study, we analyzed prospectively collected data of 187 patients with a mean follow-up period of 5.9 years. First, we found that serum bilirubin, ALP, GGT, AST, ALT, and IgM levels most prominently decreased within the first 3 months of UDCA therapy. These laboratory parameters continued to decrease gradually, with the maximum response seen at either 6 months or 1 year. Second, we found that the Paris, Barcelona, Toronto, and Ehime definition applied at 3, 6, and 12 months all significantly buy BGJ398 discriminated the patients

in terms of long-term outcome, whereas no significant association was found with the Rotterdam definition (Table 3 and Fig. 3). Finally, we found that biochemical response at the sixth month can more accurately identify patients with good or poor prognosis compared with that at 1 year. The long-term evolution of laboratory liver parameters beyond 1 year UDCA therapy has been documented, suggesting that biochemical response to UDCA can be maintained for up to 15 years.3, 16 In contrast, laboratory parameters within the first year were seldom reported in a large cohort of patients. Our cohort consisted of 187 patients who were followed at 3-month

intervals. Laboratory investigations were performed and data were collected prospectively. All of the laboratory parameters studied showed a prominent improvement in the first 3 months and then stayed relatively stable for the following months within the first ADAM7 year of UDCA treatment (Fig. 1). This led us to hypothesize that an early biochemical response as short as 3 to 6 months may be used in place of that after 1 year of UDCA therapy. We then evaluated the prognostic impact of multiple criteria in our patients. By all definitions except the Rotterdam criteria, biochemical response at 3, 6, and 12 months significantly discriminated our patients in terms of long-term outcome (Table 3 and Fig. 3). Our results tend to agree with those of the study recently published by the Paris group.14 The Paris group’s study included 165 patients with early PBC, and no significant association was found between the long-term outcomes and the Rotterdam definition. Since the Rotterdam criteria have been demonstrated to be more potent prognostic indicators of long-term outcome in late rather than early stages of PBC,8 they may not be applicable in a cohort of patients that contains high proportions of early PBC.

5% experienced single adefovir, 120% experienced single lamivudi

5% experienced single adefovir, 12.0% experienced single lamivudine, 49.4% experienced both adefovir and lamivudine, and 15.8% experienced adefovir/lamivudine plus telbivudine/entecavir). Only four patients with rtA181T were antivirals-naive. HBV genotype C/B were 93.0%/7.0% for rtA181T positive patients, and 84.6%/15.4%

for rtA181T negative patients (P <0.01), suggesting there was a positive link between rtA181T with genotype C HBV. Most but not all rtA181T led to sW172* (stop codon) mutation on overlapping S-gene and coexistence of rtA181T/sW172* with wild-type sequence was frequently detected (22.0% presented as sW172* alone, 69.9% presented GDC-0449 research buy as sW172* concomitant with the wild-type, 5.7% presented as sW1 72* with sW1 72/L or sW172S, etc). Phenotypic analysis of representative rtA181T/sW172* strains showed that the 50% effective concentration (EC50) values of adefovir for the mutants were 1.8-fold to 2.9-fold higher than that of wild-type strain. By contrast, the EC50 of adefovir for rtA1 81V or rtN236T mutants was at least 3.5-fold higher than that of wild-type strain. A defect in HBsAg secretion and a decreased replication capacity of rtA181T Selleckchem GPCR Compound Library (sW172*) strain were observed in comparison with wild-type strain in vitro; while no significant difference in average serum HBsAg and HBV DNA levels was observed between patients with and without rtA181T/sW172*. Conclusions: The emergence of HBV rtA181T mutation is closely

associated with adefovir and lamivudine exposure, but it may not directly cause adefovir resistance. The clinical significance of rtA181T should be properly interpreted. Disclosures: The following people have nothing to disclose: Xiaodong Li, Yan Liu, Liming Liu, Pan Zhao, Jiuzeng Dai, Zengtao Yao, Shaojie Xin, Dongping Xu Introduction: in chronic Hepatitis B (CHB), loss of hepatitis B surface antigen (HBsAg) and seroconversion to anti-HBs is generally considered as the ultimate goal of antiviral therapy. New combination therapy of Pegylated

interferon (PegIFN) with potent HBV Inhibitors such as tenofovir (TDF) is assessed in order to Cyclin-dependent kinase 3 improve the rate of HBsAg loss. The HBsAg gene contains the “a determinant” epitope located within the major hydrophilic region (MHR). In this study we investigate the S-gene variability of patients at baseline of PegIFN plus TDF combination therapy in order to determine the role of HBsAg variants on response to treatment. Methods: CHB patients received 180 μg of Peg-IFN/week plus 300 mg of TDF /day during 48 week. Patients were seen every 3 months. Sustained virologic response (SVR) was defined as HBV DNA< 2000UI/mL 48 weeks after end of therapy. Non-sustained virologic response (N-SVR) was defined as HBV DNA > 2000 UI/mL 48 weeks after end of therapy. HBs Ag-encoding gene from each patient’s serum at baseline was PCR-amplified, cloned and sequenced. At mean of 17 clones per patient were analysed. Results: Forty CHB patients were included in this study.

5% experienced single adefovir, 120% experienced single lamivudi

5% experienced single adefovir, 12.0% experienced single lamivudine, 49.4% experienced both adefovir and lamivudine, and 15.8% experienced adefovir/lamivudine plus telbivudine/entecavir). Only four patients with rtA181T were antivirals-naive. HBV genotype C/B were 93.0%/7.0% for rtA181T positive patients, and 84.6%/15.4%

for rtA181T negative patients (P <0.01), suggesting there was a positive link between rtA181T with genotype C HBV. Most but not all rtA181T led to sW172* (stop codon) mutation on overlapping S-gene and coexistence of rtA181T/sW172* with wild-type sequence was frequently detected (22.0% presented as sW172* alone, 69.9% presented AZD2014 ic50 as sW172* concomitant with the wild-type, 5.7% presented as sW1 72* with sW1 72/L or sW172S, etc). Phenotypic analysis of representative rtA181T/sW172* strains showed that the 50% effective concentration (EC50) values of adefovir for the mutants were 1.8-fold to 2.9-fold higher than that of wild-type strain. By contrast, the EC50 of adefovir for rtA1 81V or rtN236T mutants was at least 3.5-fold higher than that of wild-type strain. A defect in HBsAg secretion and a decreased replication capacity of rtA181T PLX4032 chemical structure (sW172*) strain were observed in comparison with wild-type strain in vitro; while no significant difference in average serum HBsAg and HBV DNA levels was observed between patients with and without rtA181T/sW172*. Conclusions: The emergence of HBV rtA181T mutation is closely

associated with adefovir and lamivudine exposure, but it may not directly cause adefovir resistance. The clinical significance of rtA181T should be properly interpreted. Disclosures: The following people have nothing to disclose: Xiaodong Li, Yan Liu, Liming Liu, Pan Zhao, Jiuzeng Dai, Zengtao Yao, Shaojie Xin, Dongping Xu Introduction: in chronic Hepatitis B (CHB), loss of hepatitis B surface antigen (HBsAg) and seroconversion to anti-HBs is generally considered as the ultimate goal of antiviral therapy. New combination therapy of Pegylated

interferon (PegIFN) with potent HBV Inhibitors such as tenofovir (TDF) is assessed in order to Rolziracetam improve the rate of HBsAg loss. The HBsAg gene contains the “a determinant” epitope located within the major hydrophilic region (MHR). In this study we investigate the S-gene variability of patients at baseline of PegIFN plus TDF combination therapy in order to determine the role of HBsAg variants on response to treatment. Methods: CHB patients received 180 μg of Peg-IFN/week plus 300 mg of TDF /day during 48 week. Patients were seen every 3 months. Sustained virologic response (SVR) was defined as HBV DNA< 2000UI/mL 48 weeks after end of therapy. Non-sustained virologic response (N-SVR) was defined as HBV DNA > 2000 UI/mL 48 weeks after end of therapy. HBs Ag-encoding gene from each patient’s serum at baseline was PCR-amplified, cloned and sequenced. At mean of 17 clones per patient were analysed. Results: Forty CHB patients were included in this study.

Ltd, Science & Technology Systems Inc, Bruker Daltonics K K,

Ltd., Science & Technology Systems Inc., Bruker Daltonics K. K., for their kind cooperation during this study. “
“Although I am not aged by current criteria, in my formative years as a junior investigator, I remember long hours in the library searching for references. There was no PubMed; instead, a book called IndexMedicus was RG7204 price searched for topics relevant to a field of research, or an information expert in the library was asked to perform a computerized search for a fee. Once articles of interest were identified, they were copied in the library

(often at a cost of $0.05/page). Copy machines were crucial for obtaining the articles. Book binding often precluded laying the book flat and interfered with accurate copying near the seam of the binding. Articles were then read, further references were identified, and this prompted additional trips to the library and p38 MAP Kinase pathway repetitive use of the copying machine. Obtaining and managing references for grants and articles was costly, tiresome, and exasperating. Relevant articles were so difficult to identify and retrieve that senior investigators could often play one-upmanship by quoting pertinent publications of which others were simply unaware. Currently, we can receive an electronic

table of contents, download articles as PDF files, and print or read them on our computer monitor; alternatively, we can run computer searches on PubMed, locate the relevant article, and download the PDF file. Considerable information is now readily available in a real-time, efficient manner. Because of the increasing number of journals and articles, the current

challenge is focusing and managing the search process. However, for access to many recent articles, an individual or institutional subscription to the journal is needed. This fact still poses a barrier to obtaining critical information. Indeed, I am currently writing a grant (still a painful, time-intensive experience), and several articles that I needed to review for emerging and evolving concepts were not available because neither I nor the institution had a subscription. This experience was frustrating and emphasized that barriers between the consumer and scientific information still exist. This problem was meant to be solved by the development of a process for open access to scientific information Carnitine palmitoyltransferase II (the availability of articles online without fees or subscriptions), but obviously universal open access has yet to be obtained. The driving force for open access has been the World Wide Web, which has facilitated a shift from print-only journals to parallel print and electronic formats. Two types of open access now exist: an article can be published in a truly open access journal such as a Public Library of Science (PLoS) journal1, 2 or in a closed access journal with subsequent deposition by the author in an open access forum such as PubMed Central. Often, this second scenario results in delayed open access.

Ltd, Science & Technology Systems Inc, Bruker Daltonics K K,

Ltd., Science & Technology Systems Inc., Bruker Daltonics K. K., for their kind cooperation during this study. “
“Although I am not aged by current criteria, in my formative years as a junior investigator, I remember long hours in the library searching for references. There was no PubMed; instead, a book called IndexMedicus was see more searched for topics relevant to a field of research, or an information expert in the library was asked to perform a computerized search for a fee. Once articles of interest were identified, they were copied in the library

(often at a cost of $0.05/page). Copy machines were crucial for obtaining the articles. Book binding often precluded laying the book flat and interfered with accurate copying near the seam of the binding. Articles were then read, further references were identified, and this prompted additional trips to the library and JNK inhibitor chemical structure repetitive use of the copying machine. Obtaining and managing references for grants and articles was costly, tiresome, and exasperating. Relevant articles were so difficult to identify and retrieve that senior investigators could often play one-upmanship by quoting pertinent publications of which others were simply unaware. Currently, we can receive an electronic

table of contents, download articles as PDF files, and print or read them on our computer monitor; alternatively, we can run computer searches on PubMed, locate the relevant article, and download the PDF file. Considerable information is now readily available in a real-time, efficient manner. Because of the increasing number of journals and articles, the current

challenge is focusing and managing the search process. However, for access to many recent articles, an individual or institutional subscription to the journal is needed. This fact still poses a barrier to obtaining critical information. Indeed, I am currently writing a grant (still a painful, time-intensive experience), and several articles that I needed to review for emerging and evolving concepts were not available because neither I nor the institution had a subscription. This experience was frustrating and emphasized that barriers between the consumer and scientific information still exist. This problem was meant to be solved by the development of a process for open access to scientific information Liothyronine Sodium (the availability of articles online without fees or subscriptions), but obviously universal open access has yet to be obtained. The driving force for open access has been the World Wide Web, which has facilitated a shift from print-only journals to parallel print and electronic formats. Two types of open access now exist: an article can be published in a truly open access journal such as a Public Library of Science (PLoS) journal1, 2 or in a closed access journal with subsequent deposition by the author in an open access forum such as PubMed Central. Often, this second scenario results in delayed open access.

7G) Unfortunately, by 6 hours a majority of Lys-Cre Ron TKfl/fl

7G). Unfortunately, by 6 hours a majority of Lys-Cre Ron TKfl/fl mice were moribund or dead and adequate blood could not be collected for ALT analysis. Importantly, however, at 6 hours ALT levels in Ron TKfl/fl control plasma were significantly higher than Alb-Cre Ron TKfl/fl plasma, suggesting protection of the TK−/− hepatocytes. TUNEL staining was PD-1 antibody inhibitor performed on liver sections at 5 hours to assess the level of apoptosis (Fig. 7D-F). Alb-Cre Ron TKfl/fl liver had statistically lower levels of TUNEL-positive cells followed by control Ron TKfl/fl and Lys-Cre Ron TKfl/fl livers (Fig. 7H). This result is consistent with western analyses for active (cleaved) caspase-3 observed

in liver lysates with the lowest levels of active caspase-3 detected in the Alb-Cre Ron TKfl/fl livers (Supporting Information Fig. S2). To test for survival differences, mice from each group were allowed to proceed until death Buparlisib mw from ALF. Kaplan-Meier survival curves (Fig. 8A) clearly show that Lys-Cre Ron TKfl/fl mice have a significantly shorter survival time. The mean survival time of each genotype is depicted

in Fig. 8B. Although Fig. 7 demonstrates protection from hepatocyte apoptosis and liver injury in the Alb-Cre Ron TKfl/fl mice compared to the other genotypes, overt survival of the Alb-Cre Ron TKfl/fl mice was longer than the Ron TKfl/fl mice but was not statistically different (P = 0.07). Here we dissected the role of Ron receptor TK in an endotoxin-induced model of acute liver failure to further studies

demonstrating that mice with a global deletion of Ron TK had a protected liver injury phenotype.16 Examination of hepatocytes and Kupffer cells showed expression of Ron in both, and importantly, ex vivo experiments showed Ron signaling is critical for both suppressing hepatotoxic Kupffer cell cytokine production and for sensitizing hepatocytes to Kupffer cell-derived products such as TNF-α. Together with in vivo experiments using mice with either hepatocyte- or Kupffer cell-specific deletion of Ron TK, we determined STK38 that Ron TK signaling in both cell types has important effects on hepatocyte survival following exposure to endotoxin in this model of acute liver failure. However, the cell type likely responsible for Ron-dependent hepatic protection in this liver injury model is the hepatocyte, given that lack of Ron signaling in hepatocytes ex vivo and in vivo is sufficient to afford a hepatocyte survival benefit. Following stimulation with LPS, TK−/− Kupffer cells have altered cytokine production ex vivo compared to TK+/+ Kupffer cells, with the most significantly elevated cytokines being IL-1ra (2.5-fold), IL-6 (2-fold), TIMP-1 (1.5-fold), MCP-1 (3.5-fold), and MIP-2 (1.9-fold). A potential mechanism for these perturbations is increased NF-κB signaling in the Ron-deficient state.