Broken canines were considered a significant health issue in 2 of 17 cases, resulting in depredation in one case. Our data support the premise that broken canines do not usually represent a serious health issue and are usually not related to HTC. The assumption that broken canines lead

to HTC appears invalid and may result in tigers being unnecessarily removed from the wild by managers. Similar results have been found for lions and the trend may be true for other large cats and carnivores as well. “
“There is an increasing awareness that PLX-4720 chemical structure adaptive differences among local populations may affect the success of translocation programmes. A mismatch in habitat quality of the target localities and in the local adaptations of the translocated individuals may reduce the success rate of the translocation programme. The green toad Bufo viridis is the most threatened amphibian in Sweden and has been the focus of an extensive translocation programme of eggs, tadpoles and juvenile toads to several localities with apparently favourable conditions for green toads. However, the success

of these measures has been poor. In this study, we investigated the extent of local adaptation in the green toad by examining population divergence and the effect of thermal and saline conditions on larval performance in four Scandinavian populations. GS-1101 in vitro In a common garden experiment, we measured larval survival and development as well as the occurrence of spinal deformations. In addition, we quantified pond temperature and water salinity,

two important environmental variables for larval performance in anurans in the breeding ponds as well as in seven additional localities included in the conservation programme. We found significant variation among the localities in water temperature and salinity, and significant among-population divergence in larval life history traits and spinal deformations, including both trait means and plastic responses to salinity and temperature. The available evidence suggests that at least part of this divergence is adaptive. We did not find direct support for local adaptation affecting the success of the translocations, however, we argue that the population origin and the impact of rearing conditions on the fitness-related Thalidomide larval traits should be taken into account in the introduction measures of the Swedish green toad conservation programme as well as in translocation programmes in general. “
“Invasive rats (Rattus spp.) are renowned bird predators and have been identified as a leading cause of island bird population declines and extinctions. Recently, new questions have been raised regarding the mechanisms and the severity of impact of invasive rat predation on bird populations. We investigated the predatory capacity of the invasive black rat Rattus rattus on bird eggs using captive trials on wild-trapped individuals.

However, the bioavailability of cyclosporine varies considerably depending on patient population this website (ranging from <10% in liver transplant patients to 89% in some kidney transplant patients).18 Therefore, the effect of telaprevir on cyclosporine concentrations in liver transplant patients may differ from that observed in this healthy volunteer study, and close monitoring of cyclosporine concentrations to guide individual dose adaptations would be necessary

during coadministration. The decrease in hepatic clearance and increase in t½ of both cyclosporine and tacrolimus upon telaprevir coadministration suggests that systemic clearance of these immunosuppressants was also reduced by telaprevir. The effect of telaprevir on hepatic transporters that could have contributed to lower clearance or enhanced absorption is unknown. Notably, in this study the effect of steady-state telaprevir on the PK of cyclosporine or tacrolimus was evaluated only at single doses of these immunosuppressants.

Because the elimination half-lives increased significantly for both cyclosporine and tacrolimus when telaprevir was coadministered, without proper adjustment of dose and dosing interval of these immunosuppressants, further increases in blood exposure may occur when multiple doses of these drugs are coadministered with telaprevir. However, studies of telaprevir with multiple doses of cyclosporine and tacrolimus have not been performed. The effects of

telaprevir on cyclosporine and tacrolimus C59 wnt exposure were similar to that reported for human immunodeficiency virus (HIV) protease inhibitors known to be potent CYP3A inhibitors, where significant reductions in dose and/or dosing interval of immunosuppressants were needed to achieve the desired range of trough concentrations, based on frequent monitoring of trough concentrations of the immunosuppressants.25 For example, addition of lopinavir/ritonavir (n = 7 patients) reduced tacrolimus Non-specific serine/threonine protein kinase dose by 99% to maintain tacrolimus concentrations within the therapeutic range.26 Similarly, during coadministration of Highly Active Antiretroviral Therapy (HAART) regimens with ritonavir-boosted HIV protease inhibitors, daily cyclosporine doses were reduced by 80%-95% to maintain cyclosporine exposure at pre-HAART levels. Because of the flat absorption/elimination profiles of cyclosporine during combination with ritonavir-boosted HAART therapy, cyclosporine exposure could be reliably monitored long-term by measuring cyclosporine trough concentrations.27 Treatment of posttransplant patients coinfected with HIV/HCV with antiretrovirals and telaprevir could be even more challenging, depending on the drugs involved. Telaprevir levels are not significantly affected by ritonavir28; however, whether the net effect of antiretroviral drugs on cyclosporine and tacrolimus PK would be similar or different is hard to predict, as these drugs may have their own effects.

0 Tesla MRI. We surveyed the morphology of the MCA at the occluded segment. Symptoms, the presence of other stenotic arteries, and atherosclerosis risk factors were compared for patients grouped by different findings on HR-MRI. MCA occlusions were classified into the following two groups: plugged MCA (13/20) with a clear view of the MCA trunk or vanishing MCA (7/20) with no MCA trunk visible in the Sylvian cistern. The presence of other stenotic arteries was more

frequent in the plugged MCA group than in the vanishing MCA group. HR-MRI can characterize the morphology of pathologic segments of chronic unilateral MCA occlusions in vivo. In chronic MCA occlusion, morphological analysis using HR-MRI may enhance the effort to assess the etiology in company with the angiographic finding. “
“Acute stroke from intracranial internal carotid Opaganib molecular weight DAPT order artery (ICA) occlusion can occasionally resemble angiographic cervical ICA dissection which may cause delays in endovascular acute ischemic stroke treatment. To determine the angiographic characteristics

of the phenomenon of “pseudodissection” and its clinical implications in acute ischemic stroke endovascular treatment. Retrospective analysis of angiographic and clinical data from 31 patients with ischemic acute stroke secondary to intracranial ICA occlusion, treated with endovascular therapy at two University-affiliated institutions, was performed. Pseudodissection was defined as angiographic appearance of typical cervical ICA dissection with evidence of normal inner vascular wall upon further catheter exploration. Angiographic appearance pseudodissection was identified in 7 out of 31 patients (22.6%). Six patients had guide catheters placed proximal to pseudodissection in anticipation of stent placement for treatment of ICA dissection. All 7 patients had further exploration of the presumed dissected segment (6 microcatheter, 1 diagnostic catheter) which demonstrated normal vascular inner wall. The

clot was located more much commonly in the petro-cavernous segment in the pseudodissection patients (5/7, 71%). Carotid terminus clot was more common in ICA occlusion patients than pseudodissection patients (18/24, 75% vs. 2/7, 29% respectively, P < .0001). Recanalization was less common in pseudodissection patients compared to ICA occlusion patients (3/7 and 21/24 respectively, P = .029). Early recognition of pseudodissection in the ICA is important in the setting of acute ischemic stroke to avoid delay in treatment of intracranial ICA occlusion. "
“Dolichoectasia (DE) is a vasculopathy that consists of abnormal elongation and dilatation of arteries. The objective of this study is to evaluate the frequency of DE in an unselected population and assess different diagnostic methods. The Northern Manhattan Study is a multiethnic population based cohort of stroke-free participants. The definition proposed for DE was total cranial volume (TCV)-adjusted arterial diameter ≥2 SD.

6±2.2 mg/day in 50 patients) or propranolol group (mean dose 153.5± 100.2 mg/day in 49 patients). After randomization, 8 patients and 11 patients AZD6244 mouse were dropped out in carvedilol and propranolol group, respectively. The response was defined to achieve a fall in HVPG to < 12 mmHg or a 20% reduction from baseline values 6weeks after treatment. Results: There were no significant differences between carvedilol and propranolol group in age, sex, etiology, Child-Turcott-Pugh score, MELD score, HVPG, presence of ascites and baseline serum parameters. In per-protocol analysis,

the response rate in carvedilol and propranolol group was 54.8% (23/42) and 45.2% (16/38), respectively (p=0.258). In intent-to-treat analysis, the response rate in carvedilol and propranolol group were 46.0% and 32.7%, respectively (p=0.174) and the mean decrease of HVPG was 15.6±18.1% and 8.1 ±30.1%, respectively (p=0.188). There was no significant difference in adverse events between two groups. Conclusions: In this interim analysis, low dose of carvedilol showed similar efficacy in reducing portal pressure compared to propranolol in cirrhotic AZD6738 in vitro patients with severe

portal hypertension. This study was entered in the Clinical Research Information Service (CRiS) Clinical Trial Registry (KCT0000102). Disclosures: The following people have nothing to disclose: Joo Hyun Sohn, Tae Yeob Kim, Soon Ho Um, Yeon Seok Seo, Soon Koo Baik, Moon Young Kim, Jae Young Jang, Soung Won Jeong, Young Seok Kim, Sang Gyune Kim, Dong Joon Kim, Ki tae Suk, Woo Kyoung Jeong Ribavirin is a synthetic guanosine ifoxetine analogue with mild, transient antiviral effect on hepatitis C virus (HCV) replication, that maintains biochemical and histological improvements in chronic hepatitis C patients not responding to standard treatment with interferon-alfa/ribavirin (Hepatology 2003; 38: 66).

We designed a proof-of-concept trial to evaluate whether maintenance treatment with ribavirin in non-responder hepatitis C virus (HCV) cirrhosis patients is associated to a reduction in portal pressure. Patients: 42 patients with genotype 1 HCV cirrhosis and portal hypertension (hepatic venous pressure gradient, HVPG, >6 mmHg) were randomized to receive for 6 months ribavirin (1000-1200 mg/day) or colchicine (0.5 mg/12 h) in open-label conditions (NCT00840489). We studied before and at the end of treatment splanchnic and systemic hemodynamics, aminotransferases, and HCV viremia. Malonyldialdehyde (MDA) was measured in hepatic vein as a surrogate of oxidative stress and inflammation. Results: Ribavirin significantly decreased HVPG (Table) and calculated hepatic vascular resistance. HVPG decreased by −7.8±15% in the ribavirin group, and increased by +13.7±36% in the colchicine group (p<0.01). Systemic hemodynamics did not change in either group. Ribavirin reduced hemoglobin (from 13.8±1.8 to 12.0±1.9 g/dl, p<0.

[9] Especially, the latter has been attributed to the deficits in motion processing, such as motion aftereffect prolongation,[10] and a decreased ability to detect coherent motion.[11, 12] fMRI relies on the measurement of altered metabolic requirements

that are influenced by neuronal activity. The highly complex mechanism underlying this process of neurovascular coupling is not completely understood, buy Quizartinib but is believed to be based on local changes in cerebral blood flow, arterial and venous cerebral blood volume, and cerebral metabolic rate of oxygen utilization, among others. Thereby, fMRI detects neuronal activity indirectly through the blood oxygenation level dependent (BOLD) effect,[13] and offers a detection of brain activation patterns with high spatial Sotrastaurin research buy resolution. While fMRI has been used to characterize the visual system in healthy humans,[14] similar studies in migraine patients are rare and the results are conflictive. To date, only one previous study has performed MRI with emphasis on interictal motion processing and found that compared with healthy controls, migraine patients showed significantly stronger activation

in the left middle-temporal complex.[15] fTCD assesses vasomotor reactivity within the arterial territory of supply: a task-specific neuronal activation causes an increase in local cerebral blood flow. This method has been applied in migraine patients during visual stimulation showing – among other findings – a greater cerebrovascular response in the middle and posterior cerebral arteries in migraineurs with lesser habituation.[3, 16] Even though Prostatic acid phosphatase lateralization

is a typical clinical feature of migraine, this aspect has been analyzed less frequently in electrophysiological visual processing and cerebral blood flow studies, and the few published studies yielded inconclusive results. While several reports with different techniques did report an interattack asymmetry of findings, a consistent relationship between the side of headache or aura and interictal distribution of functional findings has not been demonstrated.3,17-19 One obvious methodological difference between studies of the visual areas involved in motion perception in migraine patients is the use of a variety of visual stimuli, such as moving dots, rings, gratings, or a black/white checkerboard. As in previous studies,[3, 20] we chose to use a complex, moving, colored visual stimulus resulting in maximum activation of the primary and secondary visual cortices and leading to vertical optokinetic stimulation. Optokinetic stimulation can cause motion sickness due to the mismatch of visual and vestibular perception in otherwise healthy individuals.[21] Migraine sufferers, in turn, have a heightened vulnerability to motion sickness even following milder vestibular stimulation.

[30] The level of infection was monitored by confocal imaging of liver sections to detect mRFP-positive cells. InsP3-Buffer-NLS was efficiently delivered and expressed in nearly 100% of hepatocyte nuclei (Fig 5A, insert). A comparable Veliparib cell line efficiency of infection was observed in InsP3-Buffer-NES animals (not shown). BrdU uptake was impaired in animals expressing InsP3-Buffer-NLS, compared to control hepatectomized (PH) animals (Fig. 5B). Of note, expression of InsP3-Buffer-NES did not significantly alter BrdU

uptake, when compared to control PH animals, although this value was significantly higher than in InsP3-Buffer-NLS animals (Fig. 5B). Additionally, liver/body weight ratio after PH was reduced in InsP3-Buffer-NLS animals, when compared to sham or PH animals (Fig. 5C). InsP3-Buffer-NES animals had a smaller liver/body weight ratio, when compared to sham animals, although this value was not significantly different from control PH animals. Indeed, IR levels in the nucleus check details were increased 24 hours after PH in PH animals, compared to sham animals, as evidenced by IHC (Fig. 5D) and immunoblotting (Supporting Fig.

2). The 24-hour time point was chosen because it is the time at which the rate of DNA synthesis reaches its peak in hepatocytes after PH.[2] Positive proliferating cell nuclear antigen labeling in PH animals confirms Alanine-glyoxylate transaminase that hepatocytes are undergoing cell proliferation under these conditions (Supporting Fig. 2). These results show that liver regeneration after PH depends on nuclear InsP3, and increased nuclear IR may contribute, at least

in part, to this process, in accord with our observations in vitro. To investigate whether either cytosolic or nuclear InsP3 participate in insulin’s metabolic actions, we analyzed blood glucose levels and liver glycogen content under control, nuclear (InsP3-Buffer-NLS), and cytosolic (InsP3-Buffer-NES) InsP3 buffering. Using one-way ANOVA with Bonferroni’s post-tests, cytosolic, but not nuclear InsP3 buffering significantly reduced blood glucose levels (Fig. 5E) and increased liver glycogen content, compared to control animals (Fig. 5F). These results are consistent with the idea that nuclear InsP3 mediates insulin’s effects on liver regeneration, but is unrelated to insulin’s metabolic actions. The effects of Ca2+ on hepatocyte proliferation are closely related to the subcellular compartments where it is released. For instance, buffering mitochondrial Ca2+ inhibits apoptosis and accelerates liver regeneration on that basis.[30] On the other hand, buffering cytosolic Ca2+ retards liver regeneration and progression through the cell cycle after PH,[31] although there are a number of mechanisms by which cytosolic Ca2+ can increase,[10] and different sources of cytosolic Ca2+ may have different effects.

CXC chemokines are members of the chemokine superfamily. The nomenclature is based on a conserved cysteine-containing amino acid sequence

at the amino terminus of each molecule: Cilomilast C, CC, CXC and CX3C, where X is an amino acid.35 Very little is known about the C and CX3C subsets of the CXC superfamily; they possibly mediate chemotaxis of precursor T cells and natural killer cells, respectively. The CC family has multiple ligands which serve as potent chemoattractants for monocytes. Based on the presence, or absence of a glutamic acid-leucine-arginine (ELR) amino acid motif at the amino terminus of each peptide, there are two subclasses of CXC chemokines.35,36 Those possessing the ELR motif bind to the receptors CXCR1 and CXCR2, while ELR-negative chemokines bind to CXCR3, CXCR4, CXCR5 and CXCR6. The ELR-positive CXC chemokines are relevant to liver injury as CXCR1 and CXCR2 are expressed on neutrophils, SECs and hepatocytes.37 During IR injury, special signals entice neutrophils to extravasate to the hepatic parenchyma. ELR containing CXC chemokines such as macrophage inflammatory protein-2 (MIP-2), IL-8, cytokine-induced neutrophil chemoattractant

(CINC)-1 are potent chemoattractants for neutrophils.23,25,38–40 Over-expression of CXC chemokines in hepatocytes Stem Cell Compound Library lead to a swift infiltrative response by neutrophils, which then execute inflammation and injury.38,39 In contrast, neutralizing antibodies against CXC chemokines, or CXC antagonists attenuate accumulation of neutrophils and liver injury during IR.38–40 Pro-forms of CXC chemokines bound to extracellular matrix in the liver can also provide a chemotactic gradient for neutrophils following their cleavage in response to IR.25 It is important to note that CXC chemokines do not always function as chemoattractants and

are BCKDHA therefore, not irrevocably “bad.” Colleti et al. has previously reported hepatocyte proliferation in response to increasing concentrations of ERL-positive chemokines.41 Also, expression levels of CXC chemokines have been described to increase following 70% partial hepatectomy (PH); when these specific CXC chemokines were inhibited by neutralizing antibodies, liver regeneration was impaired with a significant reduction in the mass of remnant liver.42 Conversely, treatment of mice with MIP-2 accelerated hepatocyte proliferation and liver regeneration after PH.42 Moreover, genetic deletion or pharmacological antagonism of CXCR2 after hepatic IR augmented hepatocyte proliferation, and reduced injury. While the precise mechanisms underlying the pleiotropic roles of CXC chemokines after PH and in liver IR injury models are unclear, it is postulated that their divergent effects may relate to the concentration of chemokines produced in response to these specific insults.

The patient also requires consistent access to the care in real time. It is also important that there is an appropriate and regular forum to discuss patient care plans with input find more from the team members especially when a management plan is complex, has different alternatives and/or when the approach is controversial. To ensure functionality and success of the multidisciplinary care programme, the delivery of care must operate through reliable and dependable means of communication and clear documentary procedure. Finally, any such clinic requires solid administrative support and requires constant re-evaluation of its ability to deliver sound and secure care for women with IBD to ensure

its success over time. The role of the nurse coordinator in the multidisciplinary care of women with IBD is pivotal. The nurse, who is likely to be working

at an advanced practice level or with significant experience in the specialist area, is often the first point of contact for women who may be experiencing ongoing menorrhagia or other gynaecological symptoms, not resolved by visits to her general practitioner, MS-275 chemical structure or for those who are planning pregnancy or are newly pregnant and seeking advice about their obstetric care. The multidisciplinary approach to managing these women may involve many health care professionals as already described, and the haemophilia nurse is best placed to coordinate appropriate hospital visits and to facilitate the woman to attend as few visits as possible. For those presenting with menorrhagia or other gynaecological symptoms, haemophilia

nurses should Phosphatidylinositol diacylglycerol-lyase have the skills and knowledge to take a gynaecological history, to assess the main symptoms and to order the appropriate investigations, including blood tests and a pelvic ultrasound scan, in advance of the woman’s appointment in the multidisciplinary clinic. Teaching a woman to use the pictorial blood assessment chart (PBAC) [8] and to bring the completed chart to her clinic appointment offers a guide to the extent of menorrhagia. This coupled with the results of the investigations ensures that decision-making regarding treatment options, including medical management or the need for surgical investigations or interventions can take place at the first visit to the clinic [9]. The haemophilia nurse is able to offer regular monitoring of the outcomes of interventions in an ongoing relationship with the woman [10]. This does not necessarily have to involve visits to the haemophilia centre. Continued encouragement and education of affected women regarding evaluation of any medical/surgical interventions using the PBAC can be continued by telephone or mail. Lack of improvement in symptoms needs to be explored, as compliance with prescribed treatments is vital for the best possible outcomes.

Interaction with IGF-IR leads to activation of mitogen activated protein (MAP) kinase and PI3 kinase cascades that regulate genes involved in cell survival, growth, and differentiation.3 In liver cirrhosis, as result Staurosporine supplier of hepatocellular insufficiency, there is a marked reduction in the levels of IGF-I. This hormonal deficiency may play a role in the systemic metabolic derangement present in liver cirrhosis.4 In fact, treatment of cirrhotic rats with recombinant IGF-I (rIGF-I) promotes weight gain, nitrogen retention, and intestinal absorption of nutrients.5 In addition, rIGF-I has been shown to exert hepatoprotective activities

in cirrhotic rats.6 A recent pilot clinical trial showed that cirrhotic patients treated with a daily dose of rIGF-I (100 μg/kg bw) manifested a significant increase in serum albumin and an improvement of the Child-Pugh score.4 However, restoration of IGF-I ABT 199 levels

in cirrhotic patients using recombinant protein entails consumption of high doses of this molecule, making the treatment exceedingly costly. It may be envisioned that the recombinant protein might be substituted by the use of viral vectors encoding IGF-I that allow sustained expression of the transgene within the cirrhotic liver. Previously, we showed that the transfer of a recombinant Simian virus 40 vector encoding IGF-I (SVIGF-I) to a noncirrhotic liver reduced hepatocellular damage induced by subsequent administration of carbon tetrachloride (CCl4).7 However, it remained to be determined whether the injection of the vector was able to revert established liver cirrhosis. In the present article we show that administration of SVIGF-I to rats with established liver cirrhosis activates a robust tissue repair program characterized by stimulation of fibrolysis, down-regulation of profibrogenic factors, and induction of cytoprotective molecules leading to improved hepatocellular function and reduced liver fibrosis. These findings suggest that IGF-I gene transfer to the cirrhotic liver might be considered for the improvement of liver function

in patients without access to liver transplant or who deteriorate while on the waiting list for transplantation AR, amphiregulin; αSMA, α-smooth muscle actin; CCl4, carbon tetrachloride; CTGF, connective tissue growth factor; HGF, hepatocyte growth factor; HNF4α, hepatocyte nuclear factor 4 alpha; HSC, Dipeptidyl peptidase hepatic stellate cell; IGF-I insulin-like growth factor I; MAP, mitogen activated protein; MMPs, matrix metalloproteases; PDGF, platelet-derived growth factor; rIGF-I, recombinant IGF-I; TAA, thioacetamide; SVIGF-I, Simian virus 40 vectors encoding IGF-I; SVLuc, Simian virus luciferase; TGFβ, transforming growth factor beta; TIMP-1, tissue inhibitor of metalloproteinase 1; VEGF, vascular endothelium growth factor; WT-1, Wilms tumor-1. Hepatocytes, hepatic stellate cells (HSCs), and Kupffer cells were isolated from healthy and cirrhotic male Sprague-Dawley rats as described.

To date, no pharmacological treatment is approved for NAFLD/NASH. Here, we report on preclinical and clinical data with GFT505, a novel dual peroxisome proliferator-activated receptor alpha/delta (PPAR-α/δ) agonist. In the rat, GFT505 concentrated in the liver with limited extrahepatic exposure and underwent extensive enterohepatic cycling. The efficacy of GFT505 was

assessed in animal models of NAFLD/NASH and liver fibrosis (Western diet [WD]-fed human apolipoprotein E2 [hApoE2] transgenic mice, methionine- and choline-deficient diet-fed db/db mice, and CCl4-induced fibrosis in rats). GFT505 demonstrated liver-protective effects on steatosis, inflammation, and fibrosis. In addition, GFT505 improved liver dysfunction markers, decreased hepatic lipid accumulation, and inhibited proinflammatory (interleukin-1 beta,

tumor necrosis factor alpha, and F4/80) Fulvestrant molecular weight and profibrotic (transforming growth factor beta, tissue inhibitor of metalloproteinase 2, collagen type I, alpha 1, and collagen type I, alpha 2) gene expression. To determine the role of PPAR-α-independent mechanisms, the effect of GFT505 www.selleckchem.com/products/gsk126.html was assessed in hApoE2 knock-in/PPAR-α knockout mice. In these mice, GFT505 also prevented WD-induced liver steatosis and inflammation, indicating a contribution of PPAR-α-independent mechanisms. Finally, the effect of GFT505 on liver dysfunction markers was assessed in a combined analysis of four phase II clinical studies in metabolic syndrome patients. GFT505 treatment decreased plasma concentrations of alanine aminotransferase, gamma-glutamyl transpeptidase, and alkaline phosphatase. Conclusion:

The dual PPAR-α/δ agonist, GFT505, is a promising liver-targeted drug for treatment of NAFLD/NASH. In animals, its protective effects are mediated by both PPAR-α-dependent and -independent mechanisms. (Hepatology 2013; 58:1941–1952) Nonalcoholic fatty liver disease why (NAFLD) represents a spectrum of liver disorders ranging from hepatocellular steatosis through nonalcoholic steatohepatitis (NASH) to fibrosis, and irreversible cirrhosis. NAFLD is frequently observed in patients with central obesity or diabetes and its prevalence is increasing with the epidemics of type 2 diabetes and obesity, such that NAFLD is now the most common liver disease in Western countries.[1] NASH is defined by the presence of steatosis coexisting with hepatic inflammation and hepatocellular injury.[2] Although simple steatosis is generally a benign condition, NASH can have a dire prognosis resulting from concomitant evolving fibrosis[3] and progression to cirrhosis.[2] Patients with NASH have increased liver-related mortality,[4] and NASH-induced cirrhosis can result in end-stage liver disease,[5] including the development of hepatocellular carcinoma.[6] Efficacious therapeutic agents for the treatment of NASH are lacking.