10 The mechanisms responsible for disruption of hepatic insulin signaling in the insulin resistant state are under intense investigation. It has been observed by some that increased inflammation and oxidative stress are present in conjunction with hepatic insulin resistance.11 However, others suggest that lipid metabolites/intermediates, such as diacylglycerols (DAGs) and ceramides, are determinants for the development of insulin resistance (reviewed12-14). Collectively, the mechanism(s) responsible for blunted hepatic insulin action are not definitively known. To address

the relationship between hepatic mitochondrial dysfunction, GDC-0068 mouse reduced hepatic insulin action, and the potential mechanism(s), we used a murine model heterozygous (HET) for a mitochondrial trifunctional protein (MTP; the enzyme complex responsible for catalyzing the critical last three steps in long-chain fatty acid β-oxidation) gene defect previously generated by our group.2 HET-MTP mice exhibit an ∼50% reduction in hepatic

MTP protein expression and develop hepatic steatosis and systemic insulin resistance in part due to impaired mitochondrial long-chain fatty acid oxidation.2 Our novel MTP mouse model offers a unique opportunity to gain insight into the role of mitochondria in development of hepatic insulin resistance. Here, we sought to test our hypothesis that a primary defect in mitochondrial β-oxidation Oxymatrine RAD001 supplier disrupts

hepatic insulin action both in vivo and in vitro using primary hepatocytes. Furthermore, we examined potential key mechanistic causes of disruption in hepatic insulin signaling, including assessment of hepatic inflammatory pathways, as well as measurement of hepatic DAG and ceramide content and phosphatases involved in hepatic insulin signaling. ALT, alanine aminotransferase; β-HAD, beta-hydroxyacyl-CoA dehydrogenase; FFA, free fatty acids; MTP, mitochondrial trifunction protein; NAFLD, nonalcoholic fatty liver disease; TAG, triacylglycerol. The animal protocol was approved by the Institutional Animal Care and Use Committee at the University of Missouri-Columbia. Male MTP+/+ (WT) and MTP+/− (HET) mice were generated and genotype was determined by polymerase chain reaction (PCR) using primers that distinguish the mutant allele from the wildtype allele, as described.2, 15 Cages were in temperature-controlled animal quarters (21°C) with a 06.00-18.00-hour light: 18.00-06.00-hour dark cycle maintained throughout the experimental period. All animals were provided standard rodent chow (Formulab 5008; Purina Mills, St. Louis, MO) with weekly cage changes during which body mass and food intake was obtained. Mice were anesthetized (sodium pentobarbital [100 mg·kg−1]) following a 5-hour fast and killed by exsanguination by removal of the heart.

10 The mechanisms responsible for disruption of hepatic insulin signaling in the insulin resistant state are under intense investigation. It has been observed by some that increased inflammation and oxidative stress are present in conjunction with hepatic insulin resistance.11 However, others suggest that lipid metabolites/intermediates, such as diacylglycerols (DAGs) and ceramides, are determinants for the development of insulin resistance (reviewed12-14). Collectively, the mechanism(s) responsible for blunted hepatic insulin action are not definitively known. To address

the relationship between hepatic mitochondrial dysfunction, click here reduced hepatic insulin action, and the potential mechanism(s), we used a murine model heterozygous (HET) for a mitochondrial trifunctional protein (MTP; the enzyme complex responsible for catalyzing the critical last three steps in long-chain fatty acid β-oxidation) gene defect previously generated by our group.2 HET-MTP mice exhibit an ∼50% reduction in hepatic

MTP protein expression and develop hepatic steatosis and systemic insulin resistance in part due to impaired mitochondrial long-chain fatty acid oxidation.2 Our novel MTP mouse model offers a unique opportunity to gain insight into the role of mitochondria in development of hepatic insulin resistance. Here, we sought to test our hypothesis that a primary defect in mitochondrial β-oxidation next http://www.selleckchem.com/products/AZD2281(Olaparib).html disrupts

hepatic insulin action both in vivo and in vitro using primary hepatocytes. Furthermore, we examined potential key mechanistic causes of disruption in hepatic insulin signaling, including assessment of hepatic inflammatory pathways, as well as measurement of hepatic DAG and ceramide content and phosphatases involved in hepatic insulin signaling. ALT, alanine aminotransferase; β-HAD, beta-hydroxyacyl-CoA dehydrogenase; FFA, free fatty acids; MTP, mitochondrial trifunction protein; NAFLD, nonalcoholic fatty liver disease; TAG, triacylglycerol. The animal protocol was approved by the Institutional Animal Care and Use Committee at the University of Missouri-Columbia. Male MTP+/+ (WT) and MTP+/− (HET) mice were generated and genotype was determined by polymerase chain reaction (PCR) using primers that distinguish the mutant allele from the wildtype allele, as described.2, 15 Cages were in temperature-controlled animal quarters (21°C) with a 06.00-18.00-hour light: 18.00-06.00-hour dark cycle maintained throughout the experimental period. All animals were provided standard rodent chow (Formulab 5008; Purina Mills, St. Louis, MO) with weekly cage changes during which body mass and food intake was obtained. Mice were anesthetized (sodium pentobarbital [100 mg·kg−1]) following a 5-hour fast and killed by exsanguination by removal of the heart.

(Hepatology 2014;60:1717–1726) “
“The clinical course of alcoholic cirrhosis, a condition with a high mortality, has not been well described. We examined prevalence, risk, chronology, and mortality associated PF-02341066 solubility dmso with three complications of cirrhosis: ascites, variceal bleeding, and hepatic encephalopathy. We followed a population-based cohort of

466 Danish patients diagnosed with alcoholic cirrhosis in 1993–2005, starting from the date of hospital diagnosis and ending in August 2006. Data were extracted from medical charts during the follow-up period. Risk and mortality associated with complications were calculated using competing-risks methods. At diagnosis of alcoholic cirrhosis, 24% of patients had no complications, 55% had ascites alone, 6% had variceal bleeding alone, 4% had ascites and variceal bleeding, Selleck 3-deazaneplanocin A and 11% had hepatic encephalopathy. One-year mortality was 17% among patients with no initial complications, 20% following variceal bleeding alone, 29% following ascites alone, 49% following ascites and variceal bleeding (from the onset of the later of the two complications), and 64% following hepatic encephalopathy. Five-year mortality ranged from 58% to 85%. The risk of complications was about 25% after 1 year and 50% after 5 years for all patients without hepatic encephalopathy. The complications

under study did not develop in any predictable sequence. Although patients initially without complications usually developed

ascites first (12% within 1 year), many developed either variceal bleeding first (6% within 1 year) or hepatic encephalopathy first (4% within 1 year). Subsequent complications occurred in an unpredictable order among patients with Amobarbital ascites or variceal bleeding. Conclusion: Patients with alcoholic cirrhosis had a high prevalence of complications at the time of cirrhosis diagnosis. The presence and type of complications at diagnosis were predictors of mortality, but not of the risk of subsequent complications. (HEPATOLOGY 2010.) We recently reported that each year 1 in 2,000 Danish citizens aged 45–64 years is diagnosed with alcoholic cirrhosis.1 Apart from their highly increased mortality,2, 3 little is known about their prognosis because the clinical course of alcoholic cirrhosis has not been systematically described.4 In this context, we define clinical course as the evolution of alcoholic cirrhosis after diagnosis.5 The prevalence of the classic cirrhosis complications at the time of diagnosis—ascites, variceal bleeding, and hepatic encephalopathy—and their association with mortality have previously been examined.3, 6–14 However, earlier studies were hospital- rather than population-based,3, 6–10, 15 small, comprising 100 or fewer patients,8, 9 or restricted to patients diagnosed before 1980,3, 6–8 when clinical management differed from recent practice.

The study protocol conformed to the ethical guidelines of the Declaration of Helsinki (1975). All patients provided written

informed consent for the analysis of the biopsy specimens or drainage bile. The protocol for this study was approved by the ethical committee of Kanazania University, Tokyo Women’s Medical University and University of Tsukuba. Differential glycan profiling of tissue sections was performed essentially as described.21 Briefly, formalin-fixed, paraffin-embedded ICC tissue sections were deparaffinized, and the relevant tissue fragments including cancerous (n = 45) and normal bile duct epithelia (BDE) (n = 38) lesions (corresponding to 1.0 mm square and 5 μm thickness, respectively) were then scratched Selleckchem Idasanutlin from the glass slide using a needle (gauge size: 21 G) under a microscope. Total protein extracts from the scratched tissue fragments thus obtained were fluorescence-labeled with 10 μg of Cy3-succimidyl ester (SE; Amersham Ulixertinib Biosciences, Tokyo, Japan). After blocking free Cy3-SE with 0.5 M glycine in Tris-buffered saline containing 1% Triton X-100 (TBSTx), an aliquot (¼) was applied to a lectin microarray slide. Fluorescence

signals were measured on a GlycoStation scanner (Moritex Co., Tokyo, Japan). The obtained lectin microarray data were analyzed on the basis of normalized signal intensities as described,23 where the lectin showing the strongest signal intensity (max intensity) was assigned a value of 1.0. The values are presented as the median ± standard error of the mean (SEM). A two-sided Welch or Student t test was used to compare the clinicopathological data between groups. All calculations were performed using Origin version 7.5 software

for Windows (OriginLab Co., Northampton, MA). Receiver operating characteristic (ROC) curve analysis was performed to evaluate the differences between ICC and benign disease on the bases of sensitivity and specificity at various cutoff levels. An area under the ROC curve (AUC) of 1.0 indicates perfect discrimination, whereas an area of check details 0.5 indicates that the test discriminates no better than chance.24 WFA staining was performed using biotinylated WFA (Vector Co., Burlingame, UK). Detection was made with Histofine Simple Stain MAX-PO (Nichirei Co., Tokyo, Japan). The tissue sections were deparaffinized and then autoclaved to enhance the WFA reactivity. After cooling to room temperature, endogenous peroxidase was blocked by incubating the sections in methanol containing 0.3% hydrogen peroxide. The tissue sections were blocked with phosphate-buffered saline (PBS) containing 1% (wt/vol) bovine serum albumin (BSA), and the sections were incubated with 2 μg/mL of biotinylated WFA in 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid for 1 hour at room temperature. The sections were incubated with streptavidin–peroxidase reagents, reacted with 3,3′-diaminobenzidine tetrahydrochloride for visualization, and counterstained with hematoxylin.

Previously, we have shown that HGF/c-Met signaling promotes the activation and early expansion Epigenetics inhibitor of oval cells after severe liver injury in an acetylaminofluorene/partial hepatectomy rat model.12 However, the molecular mechanisms supporting adult stem cell activation are not well understood, and knowledge about the role of the HGF/c-Met pathway in this process is still limited. Recently, we and others have provided direct genetic evidence for the essential role of HGF/c-Met in hepatocyte-mediated

liver regeneration.24-26 Here, we analyzed the contribution of the c-Met-signaling pathway in stem-cell–mediated liver regeneration by utilizing liver-specific c-Met conditional knockout mice. To gain insight in the intricate nature of epithelial-mesenchymal cross-talk that defines stem cell behavior, inactivation of c-Met was achieved either in epithelial cell lineages (c-Metfl/fl; Alb-Cre+/−) or in various subsets of liver cells, including stromal cells (c-Metfl/fl; Mx1-Cre+/−), by crossing c-Metfl/fl mice with transgenic mice expressing Cre-recombinase under the control of a constitutively active albumin promoter or a ubiquitous interferon-inducible Mx1 promoter. To activate oval cells, we used a model of chronic liver injury induced by diet containing the porphyrinogenic agent, 3,5-diethoxycarbonyl-1,4-dihydrocollidine YAP-TEAD Inhibitor 1 mouse (DDC), which has been described previously.27, 28 Our results show

that the absence of c-Met caused severe damage both to hepatocytes and biliary epithelium, disrupted the balance between ECM production and degradation, and prevented stem-cell–mediated liver

regeneration. Consequently, our study establishes the HGF/c-Met-signaling pathway as an essential component of hepatic regenerative capability. AST, aspartate aminotransferase; Non-specific serine/threonine protein kinase BEC, biliary epithelial cell; DDC, a 3,5-diethoxycarbonyl-1,4-dihydrocollidine; ECM, extracellular matrix; EGF, epidermal growth factor; EpCam, epithelial cell adhesion molecule; FACS, fluorescence-activated cell sorting; HGF, hepatocyte growth factor; HNF-4α, hepatocyte nuclear factor 4-alpha; HSC, hepatic stem cell; IHC, immunohistochemistry; MMP, matrix metalloproteinase; NPC, non-parenchymal cell; PCR, polymerase chain reaction; SDF1, stromal-cell–derived factor 1; αSMA, alpha smooth muscle actin. Male 8-10-week-old Metfl/fl; Mx1-Cre+/− and c-Metfl/fl; Alb-Cre+/− mice were generated and genotyped as previously described.25, 26 Metfl/fl and c-Metwt/wt; Alb-Cre+/− mice were used as corresponding controls. For Mx1-Cre-mediated c-Met inactivation, Metfl/fl and Metfl/fl; Mx1-Cre+/− mice received three intraperitoneal injections of 300 μg of pIpC in saline at 2-day intervals, which, in the liver, was shown to result in a complete deletion of gene flanked by LoxP recombinase recognition sites.29 To induce oval cells, mice were given a diet containing 0.1% DDC (Bio-Serv, Frenchtown, NJ).

Previously, we have shown that HGF/c-Met signaling promotes the activation and early expansion LY2606368 cell line of oval cells after severe liver injury in an acetylaminofluorene/partial hepatectomy rat model.12 However, the molecular mechanisms supporting adult stem cell activation are not well understood, and knowledge about the role of the HGF/c-Met pathway in this process is still limited. Recently, we and others have provided direct genetic evidence for the essential role of HGF/c-Met in hepatocyte-mediated

liver regeneration.24-26 Here, we analyzed the contribution of the c-Met-signaling pathway in stem-cell–mediated liver regeneration by utilizing liver-specific c-Met conditional knockout mice. To gain insight in the intricate nature of epithelial-mesenchymal cross-talk that defines stem cell behavior, inactivation of c-Met was achieved either in epithelial cell lineages (c-Metfl/fl; Alb-Cre+/−) or in various subsets of liver cells, including stromal cells (c-Metfl/fl; Mx1-Cre+/−), by crossing c-Metfl/fl mice with transgenic mice expressing Cre-recombinase under the control of a constitutively active albumin promoter or a ubiquitous interferon-inducible Mx1 promoter. To activate oval cells, we used a model of chronic liver injury induced by diet containing the porphyrinogenic agent, 3,5-diethoxycarbonyl-1,4-dihydrocollidine this website (DDC), which has been described previously.27, 28 Our results show

that the absence of c-Met caused severe damage both to hepatocytes and biliary epithelium, disrupted the balance between ECM production and degradation, and prevented stem-cell–mediated liver

regeneration. Consequently, our study establishes the HGF/c-Met-signaling pathway as an essential component of hepatic regenerative capability. AST, aspartate aminotransferase; 4��8C BEC, biliary epithelial cell; DDC, a 3,5-diethoxycarbonyl-1,4-dihydrocollidine; ECM, extracellular matrix; EGF, epidermal growth factor; EpCam, epithelial cell adhesion molecule; FACS, fluorescence-activated cell sorting; HGF, hepatocyte growth factor; HNF-4α, hepatocyte nuclear factor 4-alpha; HSC, hepatic stem cell; IHC, immunohistochemistry; MMP, matrix metalloproteinase; NPC, non-parenchymal cell; PCR, polymerase chain reaction; SDF1, stromal-cell–derived factor 1; αSMA, alpha smooth muscle actin. Male 8-10-week-old Metfl/fl; Mx1-Cre+/− and c-Metfl/fl; Alb-Cre+/− mice were generated and genotyped as previously described.25, 26 Metfl/fl and c-Metwt/wt; Alb-Cre+/− mice were used as corresponding controls. For Mx1-Cre-mediated c-Met inactivation, Metfl/fl and Metfl/fl; Mx1-Cre+/− mice received three intraperitoneal injections of 300 μg of pIpC in saline at 2-day intervals, which, in the liver, was shown to result in a complete deletion of gene flanked by LoxP recombinase recognition sites.29 To induce oval cells, mice were given a diet containing 0.1% DDC (Bio-Serv, Frenchtown, NJ).

for their continuing support of the Southern Right Whale Project/Chile and the Global Greengrants Fund for funding the project. We would also like to thank Carole Carlson, Katherine Ralls, Vicky Rowntree, Mariano

Sironi, and two anonymous reviewers for their improvements to the note. Note added in proof: After the paper was accepted we learned of another sighting in central Chile. On 9 September 2011, a mother with calf was sighted and photographed off Viña del Mar (33°01′S ; 71°35′W; Pers. Comm. Sarah Allen, Ocean and Coastal Resources Selleck Navitoclax Program, Pacific West Region, National Park Service, 495 Jefferson Street, San Francisco, CA 94123, March 2013). “
“Fission-fusion dynamics seem to reflect individual decisions as well as temporal and spatial variations in the organization of groups of the same species. To understand the group dynamics of the Guiana dolphin, Sotalia guianensis, at Pipa Bay, Brazil, we investigated the three dimensions of a fission-fusion social system: (1) variation in spatial cohesion, (2) variation in party size, and (3) variation in party composition. Sampling took

place from December 2007 to February 2009 over 176 d and we analyzed the behavioral patterns of 658 groups. Within subgroups, animals remained cohesive, particularly in groups of adults and calves. Greater cohesion was also observed during resting and fission-fusion rates were higher during milling and feeding. Groups composed of adults and juveniles showed a higher dynamics index (group size variation as a function of time) than groups composed only of adults and the fission-fusion Ivacaftor ic50 rate was higher during dry periods. Guiana dolphin groups frequently changed their group size and composition every 20 min on Glycogen branching enzyme average. Taking these factors into consideration, we suggest that the Guiana dolphin demonstrates fission-fusion dynamics, a pattern of behavior similar to what has been observed in other coastal odontocete species, such as Tursiops spp. and Lagenorhynchus obscurus. “
“Killer whales produce

repertoires of stereotyped call types that are primarily transmitted vertically through social learning, leading to dialects between sympatric pods. The potential function of these call repertoires remains untested. In this study, we compared the reaction of Kamchatkan fish-eating killer whales to the playbacks of calls from the same and different pods. After the playback of recordings from a different pod, in three cases whales changed the direction of their movement toward the boat, and in three cases no changes in direction were observed. After the playback of recordings from the same pod (either from the same or a different unit within the pod), in seven cases whales changed the direction of their movement toward the boat, and in only one case no change in direction was observed. Whales remained silent after all six playbacks of recordings from a different pod, even when they changed direction toward the boat.

521) = 18.585, P < 0.001, Games-Howell post-hoc test, P = 0.001 and P = 0.022, respectively). Strong oxidants released by H. grandifolius

immediately upon wounding were below detection limits, but the addition of catalase led to a significant increase in the oxidation of DCFH after wounding (Welch’s one-way ANOVA, test statistic (3, 16.571) = 4.705, P = 0.015, Games-Howell post-hoc test, P = 0.244 and P = 0.008, respectively). Oxidant production upon wounding in the four responsive species ranged from ~3 to 15 nmol oxidants · g−1 FW. The species that released high throughput screening assay oxidants immediately after wounding were not necessarily the same as those that showed cellular localization of strong oxidants 70 min after wounding (Table 1). Palmaria decipiens, T. antarcticus, and A. mirabilis all appear to release strong oxidants

into the seawater over the course of 65 min after wounding by punching with a sterile pipette tip (Fig. 3). Peak oxidant release in all three species occurred within the first 15 min after wounding. H2O2 does not appear to be a substantial component of oxidant release over the longer term for any of these species. The addition of catalase to the medium of wounded T. antarcticus may have caused an increase in the oxidation of DCFH after wounding similar to that seen in H. grandifolius immediately after wounding. Protein nitration could not be detected in any of the four species examined INCB024360 molecular weight after wounding (P. decipiens, T. antarcticus,

A. mirabilis, and D. anceps; data not shown). Protein nitration was detected in our positive controls, indicating that the antibody was capable of hybridizing with nitrated BSA Loperamide as well as with algal nitrotyrosine residues produced by nitrating S. latissima with exogenous ONOO−. An oxidative response to wounding was common in Antarctic macroalgae. Four of five species studied released a burst of strong oxidants within 1 min of wounding and nine of 13 showed cellular oxidant production within 70 min of wounding. About half of the species studied also showed localization of strong oxidants in sham-wounded tissue. Constitutive production of strong oxidants, usually H2O2, has been documented in other algal species, including in four orders of temperate brown algae (36 of 48 species; Küpper et al. 2002). Neither the source nor the ecological function of these oxidants was experimentally addressed. The ROS may be produced by a receptor-mediated enzymatic process in response to pathogen or damage recognition (Torres et al. 2005) or the ROS may be released as a byproduct of disrupted electron transport or some other physiological trauma from wounding. Regardless of their source, ROS are generally assumed to serve as a microbial defense.

013). Similarly, among participants with rs12979860 genotyping (n = 202), clearance was higher in those with the favorable IL28B CC genotype (20%) as compared to those with unfavorable IL28B CT/TT genotypes (8%; P = 0.016). There was an association with HCV RNA level at acute HCV detection and clearance. Individuals with HCV RNA levels <4 log IU/mL were more likely to achieve spontaneous clearance (24%) as compared to those with HCV AZD0530 cost RNA of 4-6 log IU/mL (9%; P = 0.012) and those with HCV RNA >6 log IU/mL (7%, P = 0.060). There was no difference in HCV RNA level by IL28B genotype. Although

patients with unfavorable IL28B genotypes tended to have higher IP-10 levels at acute HCV detection, there was no association between IL28B genotype and IP-10 above 380 pg/mL (47% with IP-10 >380 pg/mL were TT at rs8099917). The combination of IL28B genotype and plasma IP-10 levels demonstrated spontaneous clearance as follows: low IP-10 (<380 pg/mL) and favorable rs8099917 TT IL28B genotype (22%), high IP-10 and favorable rs8099917 TT IL28B genotype (0%), low IP-10 and unfavorable rs8099917 GT/GG IL28B genotype (9%), and high IP-10 and unfavorable AP24534 datasheet rs8099917 GT/GG IL28B genotype (0%, Supporting Fig. 3). In adjusted logistic regression analyses, IL28B genotype (rs8099917TT

versus GG/GT genotype, AOR 4.22, 95% CI: 1.34, 13.28; P = 0.014) was associated with higher odds of spontaneous clearance, while higher HCV RNA level TCL was independently associated with lower odds of spontaneous clearance (<4 versus 4-6 log IU/mL, AOR 0.28, 95% CI: 0.11, 0.75 and <4 versus >6 log IU/mL, AOR 0.19, 95% CI: 0.04, 0.93). Given that plasma IP-10 levels ≥380 pg/mL were 100% predictive of not achieving spontaneous clearance, plasma IP-10 levels could not be incorporated into adjusted models of factors associated with spontaneous clearance. As a continuous variable, IP-10 levels at acute HCV detection were not associated with spontaneous

clearance (OR 0.54, 95% CI: 0.16, 1.87). Identification of factors associated with spontaneous clearance after acute HCV infection has potentially important clinical and pathophysiological significance. This study of a large sample with acute HCV showed that IP-10 levels at detection of acute infection were associated with spontaneous clearance and no patients with very high IP-10 levels (≥380 pg/mL) achieved clearance. IP-10 levels correlated with HCV RNA levels at acute HCV detection and higher HCV RNA levels (≥4 log IU/mL) predicted subsequent HCV persistence, independent of IL28B genotype. Based on these data, early therapy may be considered in individuals with high IP-10 (≥380 pg/mL) and higher HCV RNA levels, given the low likelihood of spontaneous clearance, regardless of IL28B genotype. Patients with spontaneous clearance had lower mean, but similar median, IP-10 levels at the time of acute HCV detection than those with persistence.

From October 2006 to March 2008, health care providers from the University of Massachusetts correctional health program incorporated this screening tool as part of intake medical evaluations, after a brief educational seminar regarding the potential individual and public health benefits of identifying acute HCV. To limit the burden on health care providers, the screening questionnaire was comprised of only six questions (Fig. 1). The first two addressed whether the inmate had prior HCV serologic testing. If the patient self-reported a history of a

positive HCV test, he/she was considered likely to have past infection and was referred to the medical service. If the patient reported no prior testing, unknown status,

or prior HCV seronegativity, additional questions were posed regarding new behavioral risk factors within 12 months prior to incarceration (initiation of IDU, sharing selleck chemicals Roscovitine mouse of needles or paraphernalia).14 If the patient denied risk factors for HCV acquisition, he/she was classified as low-risk. If he/she reported recent initiation of IDU and/or sharing of needles or paraphernalia, the patient was classified as high-risk. In addition, inmates who were initially diagnosed with HCV during the current incarceration or who had new seroconversion were considered high-risk for acute infection. Inmates identified as high-risk underwent in-depth interviews with the study personnel (either a registered nurse or

an infectious disease specialist). Historical data were collected in the following domains: (1) symptoms consistent with hepatitis (right-sided quadrant pain, nausea, vomiting, fatigue, jaundice, dark urine, and loss of appetite), (2) specific risk behaviors, and (3) temporal changes in behaviors. If the inmate reported recent HCV testing, medical records were requested after permission was granted. In order to evaluate elevations in aminotransferases, the patient was also asked about alcohol intake prior to incarceration. In addition, we performed laboratory testing, Atorvastatin including alanine aminotransferase (ALT), HCV antibody (EIA 2.0, Abbott Laboratories), HCV RNA levels (bDNA, Chiron), human immunodeficiency virus (HIV) antibody (Genetic Systems HIV-1 Western Blot, BioRad or OraQuick ADVANCE rapid antibody test, OraSure Technologies), and hepatitis A virus (HAV) and hepatitis B virus (HBV) serologies (i.e., HAV total antibody, HBV core antibody, HBV surface antigen, HBV surface antibody). High-risk inmates were immunized for HAV and HBV as needed. Patients were categorized according to their probability of having acute viral hepatitis using two parallel approaches as reported (Fig. 2).15 We utilized an ALT level >7 times the upper limit of normal (ULN) as our diagnostic threshold, as defined by the CDC.