For practitioners seeing patients with unexplained acute liver disease, comprehensive catalogs of DILI ALF agents are useful, but these NVP-LDE225 cost lists are only “snapshots” because prescribing practices vary geographically and temporarily.3, 24, 34 Few biologicals were implicated here, but DILI from these compounds is emerging,

including fatalities.44 Within the broad spectrum of causative agents, antimicrobials dominate.13, 16, 18, 21 Isoniazid, as monotherapy or in combination, commonly causes hepatoxicity leading to liver transplantation,17 followed by sulfur drugs, nitrofurantoin, other antibiotics, and antifungals. Amoxicillin-clavulanic and NSAIDs often cause DILI,19, 28, 45 but less commonly ALF. Perhaps the inflammation caused by the infection for which antibiotics are prescribed, predisposes the patients to develop DILI.46 Antiepileptics, antimetabolites, herbal mixtures and their derivatives, slimming potions, and illicit drugs,

have strong reputations as hepatotoxins7, 47, 48 and were well represented in our study. Statin prevalence (n ≥ 6) was unexpected, as was the occasionally long duration of exposure (median 3-6 months; range, <1 month to 36 months; see also the footnote to Table 1C). Statin hepatotoxicity is generally benign,49 but statins have been responsible for a few DILI-associated fatalities,18, 19 and atorvastatin-to-simvastatin substitution hepatitis has been reported.50 In six subjects, a statin was the only potential DILI agent—albeit sometimes with a long latency (6-36 months in three of them)—and JAK inhibitor this increases confidence in our provocative observation that awaits confirmation by others. The latency between drug use and DILI onset varies, but is usually up to 3 months although delays of up to 12 months are considered compatible.6, 16, 19, 25, 40, 45 Extended latency is the norm for nitrofurantoin51 and some other drugs,

like diclofenac. In the current study, when the cause of DILI ALF was certain, the median exposure was 2 months, but even here six cases had 6 to 10 months of latency. For isoniazid median latency was 5 months; 6-8 months in one-third of the cases. As anticipated,10, 15, 19, 21 DILI in ALF was mostly hepatocellular (77.8%) compared Ribose-5-phosphate isomerase to cholestatic and mixed reactions (19.2%) Conventional causes of cholestatic and mixed reactions (phenothiazines, macrolides, NSAIDs, carbamazepine, and phenytoin34, 52, 53) were rare. We confirmed that many drugs can cause cholestatic and mixed hepatotoxic reactions16, 19 (Table 3). Three drugs in this study have been withdrawn (bromfenac and troglitazone because of hepatotoxicity, and cerivastatin because of rhabdomyolysis), and development of the hypoglycemic agent, TAK 559, was halted. Many drugs carry warnings of hepatotoxicity (isoniazid, rifampin, ketaconazole, diclofenac, valproic acid, telithromycin, and interferon-β).

M OOI, S CHAMBERS, A THOMSON The Canberra Hospital, ACT, Australia Background: EDNAPS, in which propofol is given after the administration of other more traditional sedative agents, has been used for most endoscopic procedures at our hospital since the year 2000. Respiratory compromise related to EDNAPs, including unplanned

endotracheal intubation is much more common with gastroscopies than colonoscopies. It is not clear whether experience with this sort of sedation leads to a fall in unplanned respiratory events. Aims: To assess the safety of EDNAPS for gastroscopies over a 9 year period (2004–2012) and to determine if there is any change in unplanned respiratory events, in particular endotracheal intubation, during this period. Method: A retrospective analysis

Talazoparib clinical trial was performed of a prospectively entered Medical Emergency Team Calls(METCALLs) database of all the activated METCALLs due to respiratory compromise defined as threatened airway, respiratory arrest, oxygen desaturation <90%, respiratory rate >36 breaths or <5 breaths per minute and decreased level of consciousness. Need for endotracheal intubation post gastroscopy was recorded. The database also included patients’ demographics, indication, complications, total sedation administered and clinical outcomes after the METCALLs. Results: Of the 16393 gastroscopies performed using EDNAPS between 1st January 2004 and 1st Nov 2012, there were 18 METCALLs with an age range of 28- 84 years (mean age 61.5: 76.4% males, 23.6% females; 12 were inpatients and 6 outpatients. The ASA Tofacitinib molecular weight score for these patients were II (n = 3), III (n = 13), IV (n = 1) and one patient with no ASA score recorded. Indications for the gastroscopies were gastrointestinal haemorrhage (n = 6: 4 variceal, 2 non-variceal), dysphagia (n = 5), PEG removal (n = 1) and dyspepsia (n = 1). All activated METCALLs were associated with significant oxygen desaturation Histidine ammonia-lyase – range 51–86%. Outcomes: 11 patients made a full recovery and were discharged from the unit. 7 required

endotracheal intubation and went to the Intensive Care Unit (ICU) of whom 6 were emergency cases for upper gastrointestinal bleeding. The other patient, who had previously undergone major facialmaxillary surgery, had undergone PEG removal. One intubation occurred in 2004, 3 in 2005, 2 in 2006 and 1 in 2008 There were 2 deaths in the intubated group – one in 2004 and one in 2005. They were in a 57 yo male, ASA score III, with Child Pugh C liver disease who presented with variceal haemorrhage and was subsequently found to have a large hepatocellular carcinoma. The other occurred in an 86 year old male with ASA score IV who presented with melena due to a malignant gastric ulcer. He was subsequently found to have Stage IV metastatic lung cancer and was palliated and died 8 days post extubation.

This would assist healing of the ductal disruption and thus improve the outcome after transmural drainage. It should also lower the risk of PfC recurrence after removal of the transmural stent. However, data on the role PCI 32765 of combining transpapillary stenting with transmural drainage are limited and inconsistent. Hookey et al.7 performed endoscopic drainage of PFC in 116 patients and reported no significant difference in the success rates between patients who underwent transmural drainage alone versus those who had combined transmural and transpapillary drainage. There was a trend towards higher recurrence rates in patients with combined transpapillary and transmural

stent placement versus those who underwent transmural stenting alone (P = 0.015).The authors speculate that transmural drainage may allow the cyst-enterostomy fistula to remain patent for a longer time, even in the event of stent blockage, and the addition of transpapillary drainage may hinder this process. The transpapillary stent was placed either bridging the disruption in the pancreatic duct or within the PFC itself. However, a subgroup analysis was not done to evaluate

the effect of a bridging stent and to see whether a stent bridging the pancreatic disruption had a better outcome, as had been shown by other studies.8,9 In this issue of Journal of Gastroenterology and Hepatology, Tevino et al. report a retrospective analysis evaluating the effect of transpapillary pancreatic duct stenting on treatment KU-60019 clinical trial outcome of transmural drainage in 110 patients with PFCs.10 Patients first underwent endoscopic retrograde cholangiopancreatography (ERCP) and if a duct disruption was present, this was bridged. Transpapillary stents were not placed when the disruption could not be bridged.

Transmural drainage Erythromycin was performed in the same session; two 7 or 10 Fr stents were inserted. In patients with abscess or necrosis, a 10 Fr nasocystic catheter was placed in addition to the stents to facilitate periodic flushing. Forty (36%) of the 110 patients had successful bridging of the pancreatic duct disruption by stent. On univariate analysis, treatment success was significantly higher in those patients who, in addition to transmural drainage, underwent MPD stenting compared to those who did not undergo stenting (97.5% versus 80%; crude risk ratio = 1.22; 95% CI: 1.06–1.26; P = 0.01). In a multivariable analysis, this positive association remained significant (RR adjusted = 1.14; 95% CI: 1.01–1.29; P = 0.036), even after adjusting for etiology of pancreatitis, type and location of PFC, luminal compression at endoscopy, enteral nutrition, white blood cell count, and number of endoscopic interventions. However, recurrence of PFC was not significantly different between patients who did or did not undergo transpapillary pancreatic stenting along with the transmural drainage.

These results demonstrate that reactive oxygen species can activate proCT expression from the CGRP gene in trigeminal glia by a paracrine regulatory mechanism. We propose that this glial recruitment pathway may occur following cortical spreading depression and neurogenic inflammation to increase CGRP nociceptive actions in migraine. “
“(Headache 2010;50:769-778) Background.— Electronic medical records (EMRs) are used in large healthcare centers to increase efficiency and accuracy of documentation. These databases may be utilized for clinical research or to describe clinical practices such as medication usage. Methods.— We conducted

a retrospective analysis of EMR data from a headache Selumetinib molecular weight clinic to evaluate clinician prescription use and dosing patterns of topiramate. The study cohort comprised 4833 unique de-identified records, which were used to determine topiramate dose and persistence of treatment. Results.— Within the cohort, migraine was the most common headache diagnosis (n = 3753, 77.7%), followed by tension-type headache (n = 338, 7.0%) and cluster or trigeminal autonomic cephalalgias (n = 287, 5.9%). Physicians prescribed BMS-907351 cell line topiramate more often for subjects with migraine and idiopathic intracranial hypertension (P < .0001) than for those with other conditions,

and more often for subjects with coexisting conditions including obesity, bipolar disorder, and depression. The most common maintenance dose of topiramate was 100 mg/day; however, approximately 15% of subjects received either less than 100 mg/day or more than 200 mg/day. More than a third of subjects were prescribed topiramate for

more than 1 year, and subjects with a diagnosis of migraine were prescribed topiramate for a longer period of time than those without migraine. Conclusions.— Findings from our study selleck chemicals using EMR demonstrate that physicians use topiramate at many different doses and for many off-label indications. This analysis provided important insight into our patient populations and treatment patterns. “
“(Headache 2011;51:246-261) Objective.— To identify prognostic factors from the history and physical examination in women with tension-type headache (TTH) who are likely to experience self-perceived clinical improvement following a multimodal physical therapy session including joint mobilization and muscle trigger point (TrP) therapies. Background.— No definitive therapeutic intervention is available for TTH. It would be useful for clinicians to have a clinical prediction rule for selecting which TTH patients may experience improved outcomes following a multimodal physical therapy program. Methods.— Women diagnosed with pure TTH by 3 experienced neurologists according to the International Headache Society criteria from different neurology departments were included.

Recent studies demonstrated that CD151 gene delivery activated the PI3K/Akt pathway, induced cell migration, survival, and production of proangiogenic factors such as nitric oxide, and also promoted neovascularization after myocardial infarction in rats.11 On the contrary, mouse lung endothelial cells from CD151null mice displayed a marked reduction LDK378 purchase in pathological angiogenesis-related endothelial events, which apparently were mediated by modulation of the molecular organization of laminin-binding integrins.12 An important downstream molecule of the PI3K/Akt pathway, phosphorylated GSK, mediates the effects of Akt on cell growth, proliferation, protection from proapoptotic

stimuli, and stimulation of neoangiogenesis.32 The expression of Snail, a zinc-finger transcription factor, correlates with cancer invasion

and poor prognosis in HCC patients and is induced by the MMP family.38 In the present study, overexpression of CD151 was correlated positively with up-regulated AktSer473, Snail, and MMP9, and direct evidence has been provided for the involvement of Akt and Snail in MMP9 expression induced by overexpression of CD151. In another study, silencing of CD151 in HCCM3 up-regulated NVP-AUY922 mouse the adhesion molecule E-cadherin, and this suggested that CD151 was involved in the epithelial-to-mesenchymal transitions (unpublished data). Overexpression of CD151 prompted the accumulation of Snail in the nucleus, rather than overexpression of Snail in cytoplasm in HCC cells and HCC patients (Supporting

Information Fig. 9B,C). GSK-3β, an endogenous inhibitor of Snail transcription, can be inactivated by phosphorylated AktSer473 and is involved in the epithelial-to-mesenchymal transitions of cancer cells.39 The present study has shown that inhibition of GSK-3β up-regulates the expression of MMP9, and this indicates that the Akt/GSK-3β/Snail signal affects the expression of MMP9. In summary, overexpression of CD151 promotes the expression of MMP9 in HCCs, apparently primarily through the PI3K/Akt/GSK-3β/Snail signal (Fig. 7). A variety of molecules, such as VEGF, have been implicated in the process of angiogenesis.40 Alectinib cell line Interestingly, in the present study, we found that the expression of VEGF was hardly relevant to CD151-dependent neoangiogenesis, and this was consistent with previous reports.11, 13 Instead, MMP9 had a crucial role in CD151-dependent angiogenesis and remodeling of vessels in vitro. More importantly, the consistency of the expression level of CD151 and its relationship with MMP9 expression and angiogenesis were confirmed in an animal model. Even more significantly, we identified a role for the CD151/MMP9/angiogenesis cascade in the clinical setting of HCCs. HCC patients with CD151high were inclined to harbor higher levels of expression of MMP9 and more neoangiogenesis.

Recent studies demonstrated that CD151 gene delivery activated the PI3K/Akt pathway, induced cell migration, survival, and production of proangiogenic factors such as nitric oxide, and also promoted neovascularization after myocardial infarction in rats.11 On the contrary, mouse lung endothelial cells from CD151null mice displayed a marked reduction Akt inhibitor in pathological angiogenesis-related endothelial events, which apparently were mediated by modulation of the molecular organization of laminin-binding integrins.12 An important downstream molecule of the PI3K/Akt pathway, phosphorylated GSK, mediates the effects of Akt on cell growth, proliferation, protection from proapoptotic

stimuli, and stimulation of neoangiogenesis.32 The expression of Snail, a zinc-finger transcription factor, correlates with cancer invasion

and poor prognosis in HCC patients and is induced by the MMP family.38 In the present study, overexpression of CD151 was correlated positively with up-regulated AktSer473, Snail, and MMP9, and direct evidence has been provided for the involvement of Akt and Snail in MMP9 expression induced by overexpression of CD151. In another study, silencing of CD151 in HCCM3 up-regulated MLN0128 clinical trial the adhesion molecule E-cadherin, and this suggested that CD151 was involved in the epithelial-to-mesenchymal transitions (unpublished data). Overexpression of CD151 prompted the accumulation of Snail in the nucleus, rather than overexpression of Snail in cytoplasm in HCC cells and HCC patients (Supporting

Information Fig. 9B,C). GSK-3β, an endogenous inhibitor of Snail transcription, can be inactivated by phosphorylated AktSer473 and is involved in the epithelial-to-mesenchymal transitions of cancer cells.39 The present study has shown that inhibition of GSK-3β up-regulates the expression of MMP9, and this indicates that the Akt/GSK-3β/Snail signal affects the expression of MMP9. In summary, overexpression of CD151 promotes the expression of MMP9 in HCCs, apparently primarily through the PI3K/Akt/GSK-3β/Snail signal (Fig. 7). A variety of molecules, such as VEGF, have been implicated in the process of angiogenesis.40 Miconazole Interestingly, in the present study, we found that the expression of VEGF was hardly relevant to CD151-dependent neoangiogenesis, and this was consistent with previous reports.11, 13 Instead, MMP9 had a crucial role in CD151-dependent angiogenesis and remodeling of vessels in vitro. More importantly, the consistency of the expression level of CD151 and its relationship with MMP9 expression and angiogenesis were confirmed in an animal model. Even more significantly, we identified a role for the CD151/MMP9/angiogenesis cascade in the clinical setting of HCCs. HCC patients with CD151high were inclined to harbor higher levels of expression of MMP9 and more neoangiogenesis.

01) but did not reach statistical significance compared to the water group. Conclusion: The use of simethicone given before endoscopy provided better mucosal visibility requiring lesser this website volume of water flushes and shorter procedure time. Key Word(s): 1. Simethicone; 2. mucosal visibility; 3. endoscopy Presenting Author: OSAMU DOHI Additional Authors: ATSUSHI MAJIMA,

YURIKO ONOZAWA, TOMOKO KITAICHI, YUSUKE HORII, KENTARO SUZUKI, AKIRA TOMIE, KAZUHIRO KAMADA, NOBUAKI YAGI, YUJI NAITO, YOSHITO ITOH Corresponding Author: OSAMU DOHI Affiliations: Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Murakami Memorial Hospital Asahi University, Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine Objective: Blue LASER Imaging (BLI) is a new image-enhanced endoscopy with a laser light source developed for narrow-band light observation. The aim of this study is to evaluate the usefulness of BLI for the diagnosis of early gastric cancer. Methods: We prospectively analyzed 110

gastric lesions that were examined with both the conventional endoscopy with white-light image (C-WLI) observation and magnifying endoscopy with BLI (M-BLI) observation at Kyoto Selleckchem NVP-BGJ398 Prefectural University of Medicine between November 2012 and May 2014. The diagnostic criteria of gastric cancer using C-WLI were both an irregular margin and an irregular mucosal area. The diagnostic criteria of gastric cancer using ME-BLI were an irregular microvascular (MV) pattern and/or irregular microsurface (MS) many pattern with the demarcation line evaluated by VS classification system. The lesions were taken biopsies after M-BLI observation following C-WLI observation. We evaluated the correlations between

the diagnosis of M-BLI and that of histopathology, compared with the correlations between the diagnosis of C-WLI and that of histopathology. Results: We analyzed 110 detected lesions (23 cancers and 87 noncancers). The accuracy, sensitivity and specificity of high confidence M-BLI diagnoses were 93.6, 91.3 and 94.3%, respectively. Most of the false positive cases were depressed mucosal lesions with the histopathological diagnosis of regenerative gland in pyloric/fundic mucosa with inflammatory cell infiltration. On the other hand, the accuracy, sensitivity and specificity of C-WLI diagnoses were 88.1, 56.5 and 96.6%, respectively. Conclusion: M-BLI was useful for the diagnostic accuracy and sensitivity of early gastric cancer compared with C-WLI. Key Word(s): 1. BLI; 2. VS classification; 3.

All R remained anti-HBs+ during follow-up. 3 years post-stopping: 17/18 NR were HBeAg+ (13 with normal ALT vs. 4 with elevated ALT), only 1 patient was HBeAg-. 5 years post-stopping: 15/16 NR were HBeAg+ (7 had normal ALT vs. 8 with ALT elevation) and only 1 patient was HBeAg-. 10 years post-stopping: 7/13 NR were HBeAg+ (4 normal ALT vs. 3 had ALT elevation) and 6 achieved HBeAg seroconversion. 13 years post-stopping: 7/13 NR patients were HBeAg+ (only

1 had normal ALT) vs. 6 HBeAg- with HBeAg<1000IU/ ml and normal ALT. 5 HBeAg+ NR received/ing therapy. Methods: Total RNA was extracted from pre-treatment biopsies in patients and 5 healthy controls. HPRT1 and 7 interferon-inducible genes selleck chemicals llc (ISG15, USP18, MxA, OAS2, OAS3, viperin and CXCL10) mRNA expression was measured by quantitative realtime RT-PCR. HBV genotypes and pre-core region mutations were tested by direct sequencing. The results were compared according to genotypes, presence/absence pre-core mutations and outcome 10 years post-stopping therapy (responders vs. HBeAg+ vs. HBeAg-). Results: R had higher viperin mRNA expression and lower CXCL10 expression than NR (viperin: 16.8 vs.0.4, p<0.05; CHIR-99021 concentration CXCL10: 0.62 vs. 1.4,p<0.05). ISG expression was similar across HBV genotypes and irrespective of presence/absence of pre-core mutations.

HBeAg+ NR had higher ISG15 and CXCL10 mRNA expression than HBeAg- (ISG15: 1.96 vs. 0.41, p<0.05; CXCL10: 3.18 vs. 1.2, p<0.05), but lower viperin mRNA expression (0.52 vs. 2.63, p<0.05). Conclusions: High viperin and low CXCL10 mRNA expression in pre-treatment liver biopsy were predicting therapy response and 10 years follow-up outcomes post-IFN based therapy in immunotolerant CHB patients. Disclosures: Ivana Carey - Grant/Research

Support: Gilead, BMS, Roche; Speaking and Teaching: BMS Kosh Agarwal – Consulting: Boehringer-Ingelheim The following people have nothing to disclose: Kate Childs, Sanjay Bansal, Sarah Tizzard, Matthew J. Bruce, Mary Horner, Diego Vergani, Giorgina Mieli-Vergani “
“Oxidative stress plays a pivotal role in the transition from simple steatosis to non-alcoholic steatohepatitis Dichloromethane dehalogenase (NASH). Probucol is a lipid-lowering agent with strong antioxidant properties, and is reported to be effective for the treatment of NASH in several studies. The aim of the present study was to evaluate the efficacy of probucol for the treatment of NASH with dyslipidemia. Twenty-six patients with biopsy-proven NASH accompanied by dyslipidemia were treated with 500 mg of probucol daily for 48 weeks. Body mass index, visceral fat area, liver function tests, serum lipids, fibrosis markers, ferritin, adiponectin, leptin, urinary 8-hydroxy-2′-deoxyguanosine (U-8OHdG) and elasticity were measured periodically during the study. Follow-up liver biopsy was performed in 18 patients. Serum levels of aminotransferases, total cholesterol and U-8OHdG significantly decreased (P < 0.01).

The prevalence of major and minor complications caused by the RFA procedure was 2.8% and 1.9% in the elderly group and 3.7% and 2.0% in the non-elderly group, respectively. There was no statistical difference in the prevalence of major and minor complications between the two groups. No patient died from complications in either group. Distinctive complications

in elderly patients did not occur. THE PRESENT STUDY showed that survival rates, curative effects, prognosis-related factors and complications of RFA treatment in patients over 75 years old with HCC were similar to those in patients under 75 years old. There have been many previous studies reporting the efficiency and safety of surgical treatment for HCC in elderly patients21–24 GDC 0199 and most reports have shown similar survival rates and

levels of safety when compared with non-elderly patients. However, there have been few reports investigating these points for RFA treatment of Selleck RG 7204 elderly patients. Tateishi et al. showed that there was no difference in a 3-year survival rate between patients aged over 68 years (76%) and under 68 years (79.2%) in 1000 patients treated with RFA.25 Their data was similar to our results in this study, but their definition of “elderly” was different to ours and detailed analyses were not performed. Our paper is the report, not only presenting survival rates, but also to precisely analyze the curativeness, survival-related factors, causes of death and complications of RFA in more elderly patients. Regarding survival, the cumulative survival curve in the elderly group was identical with that in the non-elderly group, and aging was not associated with survival rates in multivariate

analysis. But based on natural O-methylated flavonoid lifespan, long-term survival rates were expected to be lower in elderly patients than in non-elderly patients. It could be conceivable that this result was influenced by differences in baseline characteristics, including sex, alcohol habits, serum ALT levels and GGT levels, because these factors are associated with progression of hepatic fibrosis or carcinogenesis.26–30 As the background characteristics of both groups were different, as discussed above, we analyzed prognostic factors in each group. It was expected that the presence of comorbid diseases might be a poor prognostic factor in the elderly group, but this was not statistically associated with survival rates in either the elderly or the non-elderly groups. These results suggest that RFA treatment should be addressed proactively even if the elderly HCC patient has a comorbid disease.

L-Fabp expression decreased 10-fold following HSC activation, concomitant with depletion of LDs. Primary HSCs isolated from L-FABP−/− mice contain fewer LDs than wild-type (WT) HSCs, and exhibit up-regulated expression of genes involved in HSC activation. Adenoviral L-Fabp transduction inhibited activation of passaged WT HSCs and increased both the expression

of prolipogenic genes and also augmented intracellular lipid accumulation, including triglyceride and FA, predominantly palmitate. Freshly isolated HSCs from L-FABP−/− mice correspondingly exhibited decreased palmitate in the free FA pool. To investigate whether L-FABP deletion promotes Selleck HIF inhibitor HSC activation in vivo, we fed L-FABP−/− and WT mice a high-fat diet supplemented with trans-fatty acids and fructose (TFF). TFF-fed L-FABP−/− mice exhibited reduced hepatic steatosis along with decreased LD abundance and size compared to WT mice. In addition, TFF-fed L-FABP−/− mice exhibited decreased hepatic fibrosis, with reduced expression of fibrogenic genes, compared to WT mice. Conclusion: L-FABP deletion

attenuates both diet-induced hepatic steatosis and fibrogenesis, despite the observation that L-Fabp paradoxically promotes FA and LD accumulation and inhibits HSC activation in vitro. These findings highlight the importance of cell-specific modulation of hepatic lipid metabolism in promoting fibrogenesis in nonalcoholic fatty liver disease. (Hepatology 2013) Nonalcoholic fatty liver disease (NAFLD) encompasses a selleck compound spectrum of pathology ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis.1 Neutral lipid storage in hepatocytes, principally in the form of triglyceride, predisposes individuals to the subsequent development and progression of NASH,2 although much is still poorly understood regarding the metabolic regulation and clinical significance of distinctive storage pools of intrahepatic Protein kinase N1 lipid. Among these intracellular storage compartments, lipid droplets (LDs) have emerged as a focal point of interest.3

LDs are specialized spherical organelles composed of a core of neutral lipids surrounded by proteins known as perilipins (Plins), which play key roles in regulating aspects of intracellular trafficking, signaling, and cytoskeletal organization.4 Understanding the pathways that regulate metabolic flux in LDs is likely to provide insight into the mechanisms of lipid-mediated liver injury.5 Hepatic stellate cells (HSCs) are the major effectors of hepatic fibrogenesis, characterized in their quiescent state by abundant LDs containing predominantly retinyl esters, triglyceride, and cholesterol ester along with cholesterol, phospholipids, and fatty acids (FAs).6, 7 In the course of hepatic injury, quiescent HSCs undergo phenotypic changes including enhanced cell proliferation, loss of LDs, expression of α-smooth muscle actin (α-SMA), and excessive production of extracellular matrix (ECM).