However, complete disruption of the main pancreatic duct or non-bridging of the ductal leak in the presence of a tight stricture or obstruction are limiting factors for achieving successful endotherapy, irrespective of stent or NPD.4 In this issue Pritelivir of Journal of Gastroenterology and Hepatology, Rana et al.13 report their interesting experience of 12 years of EPF treatment. The technology used was endotherapy

with placement of transpapillary NPD after failure of initial conservative management. In their trial, all 23 patients had persistent drain outputs >50 mL/day for 6 weeks, and 16 patients had partial pancreatic duct disruption at endoscopic retrograde pancreatography. Bridging the duct was successfully

done in 15 patients. The EPF closed in 2–8 weeks with NPD placement in this subgroup, and there was no recurrence at a mean follow-up period of 38 months. However, success of EPF closure was selleck achieved in only two of six (33%) patients who had complete duct disruption. Procedure-related complications were observed in only two cases. Costamagna et al.4 have also reported results of endoscopic transpapillary NPD placement in 16 patients with postsurgical external pancreatic fistula. Technical success was achieved in 12 of 16 (75%), and fistula closure was achieved in 11 of these 12 patients after NPD placement. Cicek et al.12 reported a similar success rate in their series of 26 patients (EPF in 23 patients). Conclusively, the overall success rate of Org 27569 fistula closure in Rana et al.’s study was 17 of 23 (74%), which is comparable to other studies. The limitation of endotherapy is cases

with complete duct disruption, in which the success rate is very low and surgical management is required in most cases.12,14 It is our cautious conclusion that surgery should be considered as an initial therapy in non-bridging complete duct disruption. Recently, secretin-enhanced dynamic magnetic resonance pancreatography was developed to visualize pancreatic duct disruption and help the clinician decide whether or not to perform endotherapy.12 The timing of endotherapy in EPF is still controversial. Since conservative therapy requires prolonged hospitalization, is of considerable cost, and usually results in poor quality of life, other modalities, including endotherapy, should be encouraged. However, the morbidity and mortality of therapeutic endoscopy in critically ill patients should also be considered, and spontaneous EPF closure is obvious in a significant proportion of patients. Boerman et al.15 reported a good result of early endoscopic intervention of EPF, although they did not specify the exact time interval after necrosectomy.

The sex and age class composition of groups, the majority including all

age classes, is consistent with daytime encounters including all behaviors (Elliser and Herzing 2012). Although this resident community Volasertib of Atlantic spotted dolphins forages during daylight on bottom dwelling and schooling fish on the shallow sandbanks (Herzing 1996, 2004), the adjacent deep waters represent an additional food resource. Atlantic spotted dolphins are rarely encountered diurnally in deep water, which suggests that they exploit the variety of prey in the DSL. Another species that utilizes the DSL are Hawaiian spinner dolphins, where dolphins rest in the shallow sandy bay during the day until sunset, when they head out to deep water to forage, returning to the bay in the early morning (Norris et al. 1994). Although tiger sharks have been observed in the deep waters of the Bahamas at night with Atlantic spotted dolphins, nocturnal feeding off the edge of the sandbank appears to be an activity of all age classes of Atlantic spotted dolphins in the Bahamas to some degree. It remains unclear if Atlantic

spotted dolphins in the Bahamas are primarily (1) nocturnal feeders, with occasional instances of opportunistic diurnal feeding; (2) diurnal feeders with episodic nocturnal foraging; or (3) opportunistic with specialization based on experience or prey species availability. In the past the analysis of nocturnal foraging habits of dolphins has been determined primarily from the examination of the stomach contents of dead animals (Perrin et al. 1973, Barros JNK inhibitors and Wells 1998). The unique habitat in the Bahamas makes this area a new location for observing diurnal and nocturnal foraging habits of small delphinids. We thank the Wild Dolphin Project and all crew and volunteers involved during the time frame of this study. This research was conducted under a permit from the Bahamian Department of

Fisheries. “
“Resident (fish eating) killer whales (Orcinus orca) in the North Pacific have been the subject of long-term studies in several geographical regions. The current study examines population parameters in the southern Alaska resident population from 1984 to 2010 and develops a population model. The southern Alaska resident population ranges from southeastern Alaska through the Kodiak archipelago medroxyprogesterone and contains over 700 individuals. We follow the life histories of 343 identifiable whales in 10 pods from two clans born before and during the study. Population parameters were comparable to those of the British Columbia northern resident population during the 1970s and 1980s, except that age of maturity was approximately one year earlier. The average annual rate of increase was slightly higher in Alaska (3.5%) than for the British Columbia northern residents (2.9%) and probably represents a population at r-max (maximum rate of growth).

In expert hands, these procedures are now being performed with a low frequency of complications and with low recurrence rates. Although current methods are

time-consuming, it seems likely that the procedure will become simpler and faster as platforms are developed that permit simultaneous retraction and cutting. Another potential area is the local treatment of gastrointestinal neoplasms with agents administered via endoscopy, perhaps with guidance from EUS. Potential agents can be engineered viruses that either selectively kill malignant cells or sensitize malignant cells to chemotherapy or radiotherapy. An alternative approach is the application of immunotherapy in pancreatic cancer where an allogeneic, mixed-lymphocyte culture (cytoimplant) is injected into the cancer to initiate a strong tumor-specific immune response. Both approaches have already been used with apparent benefit in preliminary studies.37,38 Despite the above, those who see endoscopic therapy as the future of gastrointestinal surgery should heed the lessons of endoscopic therapy

for gastroesophageal reflux disease. Between approximately 1990 and 2005, various endoscopic techniques were used to narrow the lower esophagus or ‘support’ the lower esophageal sphincter using injectible agents, scarring via radiofrequency energy or the placement of superficial sutures in the gastric cardia. These techniques have largely been abandoned although there are on-going studies designed to replicate

the principles that have been applied in open and laparoscopic fundoplication. For most endoscopy suites, the number of upper gastrointestinal procedures is either static or in decline while the number of colonoscopic procedures continues to increase. The former reflects at least some reduction in endoscopy for upper gastrointestinal bleeding while the latter reflects a focus on colorectal neoplasia, sometimes supported by local and national bowel cancer screening programs. While colonoscopy is likely to be central to surveillance for colorectal cancer for some years, alternative screening options could become available that might decrease Mirabegron the need for colonoscopic procedures. For example, fecal occult blood testing is widely used for community screening but only 1 in 20 positive subjects has cancer at colonoscopy. Conceivably, the detection of DNA mutations or specific cancer-associated proteins in blood or feces could be a more sensitive and specific EX 527 clinical trial indicator of high-risk neoplasms. Other investigations such as CT colonography and MRI colonography might also have an increased role in screening, particularly if sensitivity and specificity can be improved without the preceding use of laxatives.

HSCs are liver pericytes that reside in the space between parenchymal cells and sinusoidal endothelial cells of the liver.[2] HSCs are rich in vitamin A and store nearly 80% of retinoids of the whole body in its lipid droplets in the cytoplasm.[3, 4] Interestingly, recent studies[5-15] suggest that HSCs participate in the liver immunity. In this paper, we review the recent development in HSC-mediated

immunity and the significance of these new observations. HCV represents one of the major causes of liver fibrosis. The rate of progression of liver fibrosis varies widely in the chronic HCV infection, and progresses to cirrhosis within 20 years in an estimated 20–30% of individuals with chronic HCV infection.[16] The role of HSCs in GSI-IX supplier HCV-mediated liver fibrosis has been well documented. HCV-infected hepatocytes release transforming growth factor-β1 (TGF-β1) and other profibrogenic factors that differentially modulate HSC expression of www.selleckchem.com/products/VX-770.html several key genes involved in liver fibrosis.[17] HCV infection-induced hepatocyte

apoptosis is a common feature in chronic HCV infection.[18, 19] Apoptosis results in the generation of apoptotic bodies (ABs), which are subsequently cleared by phagocytosis. Several studies showed that HSCs have the ability to engulf ABs through phagocytosis, which can trigger a profibrogenic response.[20, 21] It was reported that ABs derived from HCV-infected Huh7 cells exhibited a more pronounced effect on profibrotic genes expression in HSCs than HCV-negative ABs.[22] Besides the indirect effects of HCV on HSCs function through infected

hepatocytes, several studies[23-26] this website indicated that there is also a direct contact between HCV and HSCs. The potential interaction between HSCs and HCV is suggested by the observation that HSCs express high levels of CD81 protein,[23] a key entry coreceptor for HCV.[24] It has been demonstrated that the HCV E2 protein can directly bind to CD81 on HSC surface, inducing fibrogenic effects on HSCs.[25] In addition to HCV envelope protein, HCV core and nonstructural proteins have also been shown to affect HSC functions.[26] Recombinant HCV core and NS3 proteins could increase intracellular calcium concentration and reactive oxygen species production in activated HSCs.[26] HCV core protein could increase HSC proliferation, and NS3-NS5 protein preferentially induced pro-inflammatory cytokines in HSCs. The roles of HSCs in HCV infection-mediated liver fibrosis are summarized in Table 1. HSCs have recently been implicated to play a novel role in the liver immunity. It was reported that HSCs could induce vigorous natural killer T (NKT) cell responses in vitro and in vivo, and promote homeostatic proliferation of NKT cells.[13] In addition, HSCs could elicit antigen-specific T cells and inhibit bacterial infection in a Listeria monocytogenes infection model.

Azathioprine, 6-mercaptopurine and thiopurine s-methyltransferase levels in gastroenterology and rheumatology: a comparison of clinical practice in Australia. J Gastroenterol Hepatol 2009;24(s2):222–223. L BESWICK,1 L SOH,2 A MCFARLANE,1 DR VAN LANGENBERG1,2 1Department of Gastroenterology, Eastern Health, Melbourne, Victoria, Australia, 2Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia Background: Infliximab (IFX) infusion reactions in patients with inflammatory bowel disease

(IBD) vary from minor urticaria to anaphylaxis. Although studies have previously observed infusion reactions in up to 10–50% of patients receiving infliximab infusions, anecdotally the prevalence appears far lower than this. To minimize reactions, standard infliximab infusions run over two hours with DNA-PK inhibitor two hours of post-infusion monitoring advised, yet many studies have shown more rapid infusion protocols to be safe and cost effective. Hence in a quality improvement initiative, we aimed to evaluate current practice of administering IFX infusions in patients with IBD and assess prevalence of IFX infusion reactions at a large volume, single IBD center, then evaluate predictive factors that are associated with an increased risk of an IFX infusion reaction. Methods: A retrospective audit of all patients with confirmed IBD who received IFX at Eastern Health between 1/1/2005- 1/1/2014 was conducted.

Data encompassing JNK inhibitor demographics, IBD clinical data, the number and time duration of IFX infusions plus the frequency, management and sequelae of infusion this website reactions were extracted from hospital records. Results: 2214 IFX infusions were administered to 169 patients throughout the nine-year period. The median number of infusions per patient was 10, with median age 38 (range 19–83) and 94 (56%) males; 126

(75%) patients had Crohn’s disease; 43 (25%) patients had ulcerative colitis. The median duration of IFX infusion was 2 hours 30 minutes (door-door at infusion unit) and 1 hour 25 minutes (start-finish infusion only) for their first documented infusion compared to 2 hours 15 minutes and 1 hour 15 minutes respectively for their most recently documented infusion. The adverse reaction rate per patient was 13.6%; 18 patients classified as having a mild reaction and 5 having a serious reaction (rate per patient 3.6%, per infusion 0.2%) according to the Common Toxicity Criteria. 17/18 (94%) with a mild reaction tolerated subsequent IFX infusions when rechallenged. According to multivariate analysis, predictive factors of an IFX infusion reaction included episodic or gap >3 months in IFX dosing (OR 8.7, 95% CI [1.8, 41.4], concurrent immunomodulator OR 9.4 [1.5, 57.4], smoker at time of reaction OR 3.8 [1.01, 13.9], duration of IBD when IFX started (per year, OR 1.11 [1.04, 1.2]) (each p < 0.05), with a non-significant trend for previous adverse drug reaction(s) OR 3.2 [0.8, 13.3] (p = 0.1).

86,87 Diseases that can mimic drug-induced cholestasis, such as primary biliary cirrhosis or sepsis (bacterial or viral) should be ruled out. Evaluations should always include hepatitis and autoimmune serologies and appropriate imaging studies. On rare occasions, patients may develop symptoms on reexposure to the same medication. However, rechallenge with the suspected

drug is usually contraindicated, particularly if there is active liver injury, because severe or even fatal learn more liver injury can occur. The role of liver biopsy is controversial. Nevertheless, performing liver biopsy may be helpful when the diagnosis is not clear or when there are other complicating medical conditions. Occasionally, the pathologist will first suggest the possibility of a drug- or toxin-induced injury. A biopsy may also be useful in predicting prognosis (see a recent review88 for a more comprehensive discussion GS-1101 molecular weight of the role of liver pathology in drug-induced liver injury). Most

cases of drug-induced cholestasis will resolve with withdrawal of the offending medication and not develop chronic liver disease. A Swedish adverse drug reaction advisory committee report concluded that AST and bilirubin levels are the most important predictors of death or liver transplantation in DILI.6 In another study, the persistent use of the offending agent for >6 months

after diagnosis of DILI, predicted the development of chronic liver disease and fibrosis in liver biopsies.89 In addition to watchful waiting after stopping the suspected agent, it is important to treat pruritus when present. Severe pruritus may lead to sleep deprivation and psychological abnormalities especially in elderly patients. The pathophysiological mechanism of pruritus from cholestasis is still unknown. Suggested mechanisms include high tissue and serum bile salt concentrations, increased opioidergic tone, and alteration of serotonin neurotransmitters.90-92 A recent study has check details suggested lysophosphatidic acid as a potential mediator.93 Mild pruritus can often be managed by nonspecific measures such as emollients and warm baths and/or histamine-1–receptor blockers such as hydroxyzine and diphenhydramine due to their sedative properties. Bile acid resins (cholestyramine or colestipol) are the first-line agents in moderate to severe pruritus, particularly when associated with excoriations and disturbed sleep.94 Based on the inference that the pruritogens are excreted in bile, they function to exchange organic anions such as bile acids with chloride anions in the intestine.

RBV dose reduction was needed in 33% and blood transfusion in 16%. Infections were rare and there were no deaths. Early treatment discontinuation occurred in 24%, more often due to treatment futility (14%) than adverse events (10%). A sustained VR at week 12 post-treatment (SVR12) was achieved in 82% (95/115) of non-cirrhotics and 66% (28/42) of cirrhotics. In a multivariate logistic regression analysis, presence of cirrhosis (OR 2.75, p = 0.03, CI 1.1–6.91) Selleckchem DZNeP and non-IL28B CC (OR 11.73, p = 0.024, CI 1.39–98.69) were associated with failure to achieve SVR12. Conclusion: In this first

multi-center real-world study of clinical experience with BOC in Australia, treatment of a large well-compensated cohort with BOC demonstrated acceptable efficacy and safety data that were comparable to that in registration studies. Ku-0059436 manufacturer MA CHINNARATHA,1 M-Y(A) CHUANG,2 R FRASER,1,2 RJ WOODMAN,1 AJ WIGG1,2 1School of Medicine, Flinders University of South Australia, 2Gastroenterology and Hepatology, Flinders Medical Centre, Bedford Park, South Australia Percutaneous thermal ablation techniques [Radiofrequency Ablation (RFA) and Microwave Ablation (MWA)] are commonly used worldwide

for treating early stage primary hepatocellular carcinoma (HCC) and are considered a curative treatment in properly selected candidates. This meta-analysis aims to compare the safety and effectiveness of the two modalities. Methods: Databases (MEDLINE, EMBASE and Cochrane central) were searched from Jan 1980 to Mar 2014 for retrospective and prospective studies in humans and in English language comparing RFA and MWA. Abstracts in AASLD and EASL meetings for the past 3 years were also reviewed. Study quality was assessed using the modified Newcastle-Ottawa quality assessment scale. Primary outcome was the risk of local tumor progression (LTP); Secondary outcomes were complete ablation (CA) rate and major adverse events (AE) with these two techniques. Fixed/ random-effects model were used depending on the degree of heterogeneity and the outcomes reported using pooled odds ratio (OR) with 95% CI. Results: Overall, 10 studies (2 prospective

see more and 8 retrospective) with 1298 subjects were included. There was no difference in LTP rates between RFA and MWA [OR (95%CI): 1.01 (0.73–1.41), p = 0.9] (Fig 1). The CA rate [1.03 (0.64–1.66), p = 0.9] and major AE [0.56 (0.27–1.18), p = 0.13] were also similar between the two modalities. Subgroup analyses based on quality of studies, type of MWA generator used and treating very early or early BCLC stage HCC showed no difference in LTP rates between the two modalities. However, MWA showed lower LTP rates when treating larger/multiple tumors outside Milan criteria [1.88 (1.1–3.23), p = 0.02]. Only one prospective study compared the duration of the procedures and MWA sessions are an average 20 minutes less compared to RFA sessions.

Simple regression analysis revealed that the volumetric Neratinib proportion of each plaque type correlated significantly with the corresponding plaque-type area at the minimum lumen site. The adjusted coefficients of determination of the simple regression analyses were .782 (P < .001) for fibrous tissue, .741 (P < .001) for fibrofatty tissue, .864 (P < .001) for dense calcium, and .918 (P < .001) for necrotic core. The plaque composition at the minimum lumen site represents the volumetric composition of the entire carotid plaque that causes atherosclerotic cervical carotid artery stenosis. "
“Diffusion tensor imaging (DTI) quantifies the motion of water

within brain tissue. Inflammation leads to tissue disruption, resulting in increased diffusivity and decreased directionality. We aimed to quantify the damage within tumefactive giant brain lesions

(TGL) in multiple sclerosis (MS) using MRI and DTI methodology. Region of interest were determined on TGL and acute MS lesions to obtain metrics such as volume, apparent diffusion coefficient (ADC), fractional anisotropy (FA), axial diffusivity (λ||), and radial diffusivity (λ⊥). We identified 10 TGL in 10 patients with MS. The incidence of TGL was 2.8%. Comparing TGL to acute 16 MS lesions, DTI metrics demonstrated significantly higher ADC, λ|| and λ⊥ diffusivities and lower FA values in TGL (P <.001). Five TGL were reevaluated after Palbociclib 120 days by MRI and DTI metrics. Significant group changes were detected at 120 days: TGL volume decreased, ADC, λ|| and λ⊥ values were lower and FA was higher

(P < .01). Within the spectrum of acute MS lesions, TGL present DTI metrics of an intense acute inflammatory process. Analysis of TGL progression proposes that DTI metrics sensitively detects micro-structural changes in TGL from acute inflammation towards lesion recovery and reorganization. "
“To prospectively evaluate longitudinal changes in white matter lesions (WMLs) in migraineurs with aura, by magnetic resonance imaging (MRI), and to correlate WMLs modifications with patients’ clinical characteristics. Forty-one consecutive migraineurs with aura were followed for a mean time of 33.2 months. click here Patients underwent MRI at baseline and follow-up and were evaluated for cerebrovascular risk factors. Presence of WMLs on MRI was assessed by two neuroradiologists. WMLs were present in 26 subjects (63.4%) at baseline MRI. At follow-up a total of 8 patients had new WMLs (19.5%). There was a significant correlation between aura duration and number of new WMLs, and between the number of migraine attacks with aura and new WMLs. Our study demonstrates that in migraine with aura WMLs number can progress over time and suggests an association between aura features and WMLs progression. Studies with a higher number of patients are required to confirm these findings. “
“Recent advancement for magnetic resonance imaging (MRI) involves the incorporation of higher-field strengths.

Simple regression analysis revealed that the volumetric find more proportion of each plaque type correlated significantly with the corresponding plaque-type area at the minimum lumen site. The adjusted coefficients of determination of the simple regression analyses were .782 (P < .001) for fibrous tissue, .741 (P < .001) for fibrofatty tissue, .864 (P < .001) for dense calcium, and .918 (P < .001) for necrotic core. The plaque composition at the minimum lumen site represents the volumetric composition of the entire carotid plaque that causes atherosclerotic cervical carotid artery stenosis. "
“Diffusion tensor imaging (DTI) quantifies the motion of water

within brain tissue. Inflammation leads to tissue disruption, resulting in increased diffusivity and decreased directionality. We aimed to quantify the damage within tumefactive giant brain lesions

(TGL) in multiple sclerosis (MS) using MRI and DTI methodology. Region of interest were determined on TGL and acute MS lesions to obtain metrics such as volume, apparent diffusion coefficient (ADC), fractional anisotropy (FA), axial diffusivity (λ||), and radial diffusivity (λ⊥). We identified 10 TGL in 10 patients with MS. The incidence of TGL was 2.8%. Comparing TGL to acute 16 MS lesions, DTI metrics demonstrated significantly higher ADC, λ|| and λ⊥ diffusivities and lower FA values in TGL (P <.001). Five TGL were reevaluated after NVP-AUY922 in vitro 120 days by MRI and DTI metrics. Significant group changes were detected at 120 days: TGL volume decreased, ADC, λ|| and λ⊥ values were lower and FA was higher

(P < .01). Within the spectrum of acute MS lesions, TGL present DTI metrics of an intense acute inflammatory process. Analysis of TGL progression proposes that DTI metrics sensitively detects micro-structural changes in TGL from acute inflammation towards lesion recovery and reorganization. "
“To prospectively evaluate longitudinal changes in white matter lesions (WMLs) in migraineurs with aura, by magnetic resonance imaging (MRI), and to correlate WMLs modifications with patients’ clinical characteristics. Forty-one consecutive migraineurs with aura were followed for a mean time of 33.2 months. selleckchem Patients underwent MRI at baseline and follow-up and were evaluated for cerebrovascular risk factors. Presence of WMLs on MRI was assessed by two neuroradiologists. WMLs were present in 26 subjects (63.4%) at baseline MRI. At follow-up a total of 8 patients had new WMLs (19.5%). There was a significant correlation between aura duration and number of new WMLs, and between the number of migraine attacks with aura and new WMLs. Our study demonstrates that in migraine with aura WMLs number can progress over time and suggests an association between aura features and WMLs progression. Studies with a higher number of patients are required to confirm these findings. “
“Recent advancement for magnetic resonance imaging (MRI) involves the incorporation of higher-field strengths.

We wanted click here to test our hypothesis that TNFα plays a dual role in LPS/D-galN-induced liver injury, first acting as a proapoptotic mediator of liver damage, and later as an important hepatoprotective factor. We therefore

injected infliximab 4 hours after LPS/D-galN injection. Interestingly, a late administration of anti-TNFα indeed resulted in a loss of NS3/4A-mediated resistance (Fig. 6). This indicates that the sustained increase in intrahepatic TNFα levels seen in NS3/4A-Tg mice mediates the hepatoprotective effects of TNFα (Fig. 4). LPS is sensed in the liver mainly by TLR4 expressed on the surface of Kupffer cells, which are the liver-specific macrophages, and liver sinusoidal endothelial cells. In response to TLR4, these cells release proinflammatory cytokines such as TNFα. In

human hepatitis, intrahepatic macrophages are the main producers of TNFα. We therefore investigated the expression levels of CCL2 (monocyte chemoattractant protein 1), which represents the main chemokine involved in intrahepatic activation and recruitment of monocytes/macrophages. We found that CCL2 protein levels were enhanced both in untreated and LPS/D-galN-treated livers of NS3/4A-Tg mice as compared to the corresponding WT mice (Fig. 7). This was paralleled by a higher number of F4/80 antigen-positive cells in LPS/D-galN-treated livers of NS3/4A-Tg mice as compared to WT mice (43.70 ± 5.83 versus 28.50 ± 3.37 positive GDC-0068 supplier cells per 10 mm2 of liver, P < 0,0001, Mann-Whitney; Fig. 4B) which may be due to increased CCL2-mediated recruitment of macrophages

to the liver. Thus, the NS3/4A-mediated resistance to LPS/D-galN and TNFα/D-galN in our NS3/4A-Tg mice may be caused by increased CCL2 expression resulting in induction of TNFα production and subsequent NFκB activation, which provokes a paracrine loop with further release of TNFα and selleck inhibitor activation of NFκB. It is well known that patients with chronic HCV infection have increased serum levels of TNFα, a potent proinflammatory factor with a broad spectrum of effects. A major concern in patients with chronic HCV and rheumatoid arthritis has been that the effective block of TNFα conferred by the new class of anti-TNFα agents should have deleterious effects on the HCV infection; however, this has not been the case. On the contrary, when anti-TNFα compounds are added to SOC therapy in patients with chronic HCV, treatment results improve.9 This highly unexpected finding suggests that TNFα has effects that actually promote the viral infection. We therefore used our NS3/4A-Tg mouse model, which we have shown has a reduced sensitivity to TNFα, to elucidate these issues further. We have shown that the NS3/4A complex exerts protective effects toward hepatotoxic stimuli such as LPS/D-galN, TNFα/D-galN, and CCl4 in NS3/4A-Tg mice. All of these compounds induce liver injury, at least in part, through TNFα.