63–2.12).21 Wang et al.’s group studied PF-02341066 datasheet 98 East Asian patients, and found clopidogrel and PPI co-prescription was associated with a higher risk of re-infarction, odds ratio 1.62 (95% CI 1.01–2.59).22 Ho et al. studied 8205 patients following a diagnosis of acute coronary syndrome and found that 29.8% of patients co-prescribed a PPI and clopidogrel versus

20.8% on clopidogrel alone died or were rehospitalized (adjusted odds ratio [OR] 1.25, 95% CI 1.11–1.41).23 Finally, Juurlink et al. carried out a nested cohort-control study involving 13.636 patients following myocardial infarction and concluded that the current use of a PPI was associated with an increased risk of re-infarction (adjusted OR 1.27, 95% CI 1.03–1.57), although this was not seen for pantoprazole (adjusted OR 1.02, 95% CI 0.70–1.47).24 These studies have a number of serious shortcomings which require comment. First, Gilard and Sibbing et al.’s studies demonstrated a reduction in clopidogrel activity as determined by VASP and/or platelet aggregometry; whether this translates into a meaningful reduction in clopidogrel’s antiplatelet effect in terms of clinical outcomes is unclear. With regard to the studies demonstrating an adverse clinical outcome for patients co-prescribed a PPI and clopidogrel,

first the increase in the relative risk of cardiovascular events for patients taking PPI is very modest with odds ratios ranging from 1.25 to 1.79.20–24 Second, there were important differences between the cohort and control groups: for example in the Juurlink study, the PPI group included a statistically significantly higher rate of acute renal failure, http://www.selleckchem.com/products/Bortezomib.html congestive heart disease and diabetes mellitus (DM) with complications. Similarly, in the study by Ho et al. the PPI group also included a statistically significantly higher rate of chronic obstructive MCE pulmonary disease (COPD), DM, previous myocardial infarction, congestive cardiac failure, liver and renal disease. Despite the author’s statistical analyses, which attempted to control for these imbalances, such a study may

still result in unknown confounders, which makes attributing the adverse outcomes to PPI co-prescription problematic.20–24 Looked at from another perspective, these studies suggest that patients with multiple serious co-morbid illnesses are more likely to be at high risk of GI bleeding and therefore be prescribed a PPI.25 Third, in the Juurlink study the difference in the effect between pantoprazole and that of other PPIs is not statistically significant and the point estimate of the other PPIs lies within the 95% CI associated with the effect of pantoprazole. A formal test for heterogeneity of these odds ratios also shows no statistically significant difference (χ2 = 2.99, 1 degree of freedom, P = 0.08).26 Therefore, no conclusion should be drawn about the benefit of pantoprazole over other PPIs from this study.

63–2.12).21 Wang et al.’s group studied click here 98 East Asian patients, and found clopidogrel and PPI co-prescription was associated with a higher risk of re-infarction, odds ratio 1.62 (95% CI 1.01–2.59).22 Ho et al. studied 8205 patients following a diagnosis of acute coronary syndrome and found that 29.8% of patients co-prescribed a PPI and clopidogrel versus

20.8% on clopidogrel alone died or were rehospitalized (adjusted odds ratio [OR] 1.25, 95% CI 1.11–1.41).23 Finally, Juurlink et al. carried out a nested cohort-control study involving 13.636 patients following myocardial infarction and concluded that the current use of a PPI was associated with an increased risk of re-infarction (adjusted OR 1.27, 95% CI 1.03–1.57), although this was not seen for pantoprazole (adjusted OR 1.02, 95% CI 0.70–1.47).24 These studies have a number of serious shortcomings which require comment. First, Gilard and Sibbing et al.’s studies demonstrated a reduction in clopidogrel activity as determined by VASP and/or platelet aggregometry; whether this translates into a meaningful reduction in clopidogrel’s antiplatelet effect in terms of clinical outcomes is unclear. With regard to the studies demonstrating an adverse clinical outcome for patients co-prescribed a PPI and clopidogrel,

first the increase in the relative risk of cardiovascular events for patients taking PPI is very modest with odds ratios ranging from 1.25 to 1.79.20–24 Second, there were important differences between the cohort and control groups: for example in the Juurlink study, the PPI group included a statistically significantly higher rate of acute renal failure, FK228 congestive heart disease and diabetes mellitus (DM) with complications. Similarly, in the study by Ho et al. the PPI group also included a statistically significantly higher rate of chronic obstructive medchemexpress pulmonary disease (COPD), DM, previous myocardial infarction, congestive cardiac failure, liver and renal disease. Despite the author’s statistical analyses, which attempted to control for these imbalances, such a study may

still result in unknown confounders, which makes attributing the adverse outcomes to PPI co-prescription problematic.20–24 Looked at from another perspective, these studies suggest that patients with multiple serious co-morbid illnesses are more likely to be at high risk of GI bleeding and therefore be prescribed a PPI.25 Third, in the Juurlink study the difference in the effect between pantoprazole and that of other PPIs is not statistically significant and the point estimate of the other PPIs lies within the 95% CI associated with the effect of pantoprazole. A formal test for heterogeneity of these odds ratios also shows no statistically significant difference (χ2 = 2.99, 1 degree of freedom, P = 0.08).26 Therefore, no conclusion should be drawn about the benefit of pantoprazole over other PPIs from this study.

05). In contrast, another large retrospective study for GSK-3 phosphorylation HCC patients with tumor less than 5 cm in diameter enrolled in the Liver Cancer Study Group of Japan.[41] The results showed that HCC patients who received liver resection (n = 8010) had better survival than RFA (n = 4037) or TACE (n = 841). In the Japan study, the lesions of HCCs measuring > 3 cm were included in this study resulting incomplete ablation and the proportion

of patients with associated cirrhosis was lower in the surgical resection group than in the nonsurgically treated group. The beneficial effect of hepatectomy was due to the removal of venous tumor thrombi and complete eradication of the primary tumor with clean resection margins.[35, 42] Another similar study from the Hong Kong, China,[19] compared the survival outcome and

disease-free Selleck PR-171 survival of a total of 228 patients who underwent RFA of small (< 3 cm; n = 155) and medium (3.1–5 cm; n = 73) HCC by percutaneous or surgical approach. Percutaneous RFA approach achieved similar tumor control with lower morbidity compared with the surgical approach for patients with small HCC. In our study, during a follow-up of 40 months, there was a trend toward a higher intrahepatic recurrence in the percutaneous RFA group as well as extrahepatic metastases in the surgical hepatectomy group, but the difference was not of statistical significance (P = 0.502 上海皓元 and P = 0.611, respectively). Local recurrences after percutaneous RFA might be attributable to

insufficient ablation of the primary tumor, and/or the presence of portal or hepatic venous tumor thrombi in the adjacent liver.[43] The predominant trend of extrahepatic recurrence in the hepatectomy group was associated with the following factors: compression, separating of the primary tumor, intraoperative blood transfusion, hematogenous dissemination, and/or devascularization.[23, 44] However, RFA had significant advantages over surgical resection in causing only one major and one minor complications, less severe pain, a shorter intensive care unit stay and hospital stays (P < 0.01). These data were similar to the first large clinical experience with RFA as reported by Rossi et al.[45] and other researchers.[36, 46] Two patients underwent liver transplantation further after re-recurrence, and salvage liver transplantation is an efficacious treatment for patients with recurrent HCC and should be considered when repeated hepatic resection is not feasible.[47] There are still a few outstanding issues that are worth pursuing in future studies. First of all, the sample size of 120 patients in this study was relatively small. However, with the strong belief by oncologists and surgeons as well as patients that RFA has become a more commonly used treatment modality for HCC, we believe that a larger sample size will likely be collected for future comparison with surgical resection.

Methods: Aptamers were incubated with serum specimens and then electrophoresed on polyacrylamide gel (PAGE) and stained with GelRed. The gray value of the free aptamer band in each specimen was measured. The gray ratio of each specimen to the aptamer control was calculated. A mathematical diagnostic model was created with multivariate logistic regression analysis of gray indicators. The area under the receiver operating characteristic curve (AUC) and diagnostic performance were used to evaluate the diagnostic value of aptamers for PHC. Results: Twelve aptamers were evaluated in 72 cases of PHC and 108 cases of non-PHC (the cases of cirrhosis, hepatitis

B and normal controls were all 36). The Pembrolizumab research buy free bands of aptamer incubated with PHC specimens were usually weaker than that of non-PHC specimens, and the results of gray measurement were accorded with them. The diagnostic value of gray ratio and diagnostic model were showed in the table 1 below. This is firstly reported that aptamers against PHC serum applied in the study of diagnosis of PHC, and also PAGE combined gray analysis was firstly introduced to evaluate the diagnostic value of the aptamers. Conclusion: The Buparlisib ic50 aptamers against primary hepatic carcinoma serum are valuable in the diagnosis of primary hepatic carcinoma. Key Word(s): 1. Aptamer; 2. Serum; 3. Hepatoma; 4. Diagnosis; Aptamer Gray ratio Mathematical model AUC Sensitivity (%) Specificity MCE (%) Accuracy (%) AUC Sensitivity (%) Specificity (%) Accuracy (%) AP-HCS-9-10 0.881 76.4 83.3 80.6 0.913 86.1 86.1 86.1 AP-HCS-9-26 0.749 56.9 81.5 71.7 0.845 73.6 77.8 76.1 AP-HCS-9-31 0.768 66.7 77.8 73.3 0.853 65.1 85.5 78.3 AP-HCS-9-74 0.885 72.2 88.9 82.2 0.949 88.9 89.8 89.4 AP-HCS-9-89 0.688 43.1 80.6 65.6 0.931 81.9 90.7 87.2 AP-HCS-9-90 0.893 85.2 84.7 84.4 0.965 90.7 90.3 90.6 AP-HCS-9-132 0.862 75.0 83.3 80.0 0.918 76.4 90.7 85.0

AP-HCS-11-3 0.816 63.9 88.0 78.3 0.939 83.3 86.1 85.0 AP-HCS-11-4 0.859 72.2 85.2 80.0 0.894 79.2 80.6 80.0 AP-HCS-11-5 0.859 73.6 77.8 76.1 0.916 79.2 88.0 84.4 AP-HCS-11-6 0.847 66.1 83.4 77.2 0.942 86.1 69.8 88.3 AP-HCS-11-8 0.795 66.7 81.5 75.6 0.827 66.7 78.7 73.9 AP-HCS-11-10 0.870 69.4 83.3 77.8 0.899 80.6 87.0 84.4 Presenting Author: SHI QIU Corresponding Author: SHI QIU Affiliations: Wuhan university Objective: To investigate the expression of liver-intestine (LI)-cadherin in hepatocellular Carcinoma (HCC) by tissues microarray and explore its relationship with pathologic features of HCC patients. Methods: Seventy primary HCC resection samples with different indexing and five primary normal tissues samples were assessed by tissue microarray and immunohistochemistry based on the SP method.

(HEPATOLOGY 2011;) See Editorial on Page 1427 This work was undertaken to address two issues raised in an editorial about our previous article16: (1) testing the accuracy of HCC immunomarkers in a homogeneous series of HCCs up to 2 cm in size and (2) improving the accuracy of the panel with additional markers. To this end, we retrospectively evaluated a series of HCCs consecutively diagnosed

on core biopsy samples with a 20- to 21-gauge needle; with this material, we tested the diagnostic accuracy of a refined panel of markers (CHC, GPC3, HSP70, and GS). The performance of the panel was also evaluated according to HCC grading [grade 1 (G1) versus grade 2 (G2)/grade 3 (G3)] and sizes (≤2 versus >2 cm). 3M, three-marker; 4M, four-marker; AASLD, American Roxadustat manufacturer Association for the Study Palbociclib of Liver Diseases; CHC, clathrin heavy chain; G1, grade 1; G2, grade 2; G3, grade 3; GPC3, glypican 3; GS, glutamine synthetase; H&E, hematoxylin and eosin; HCC, hepatocellular carcinoma; HGDN, high-grade dysplastic nodule; HSP70, heat shock protein 70; LGDN, low-grade dysplastic nodule. The series

under study was composed of 20- to 21-gauge needle core biopsy samples from 86 HCCs with a cirrhotic background. They were obtained from the files of the Policlinico General Hospital (Milan, Italy) and Melegnano General Hospital (Melegnano, Italy) and were collected from 2005 to 2009. The diagnosis of HCC was made in all the cases according to AASLD guidelines.17 The diagnostic process included routine laboratory tests, serum alpha-fetoprotein measurements, and abdominal ultrasound, contrast-enhanced spiral computed tomography, or magnetic resonance imaging. The diagnosis of cirrhosis was based on histology or concordant laboratory and imaging findings. The tumor size was the largest diameter measured by imaging. The histopathological diagnosis of HCC 上海皓元 was originally made mostly after hematoxylin and eosin (H&E) staining supplemented by routine histochemical stains such as Gomori staining for reticulin, Perls’ staining for iron, and Masson trichrome staining. All the slides were preliminary revised by two expert pathologists (M.R.

and L.D.T.), and the diagnosis of HCC was confirmed after accurate morphological analysis in all cases. HCC grading was based on the available material according to Edmondson and Steiner,18 and cases were divided into two groups: well-differentiated histology (G1) and moderately to poorly differentiated histology (G2/G3). The main pathological criteria for identifying well-differentiated HCCs and distinguishing them from high-grade dysplastic nodules (HGDNs) are reported in Supporting Table 1. The series included only cases with a tumor core and material available for immunocytochemical analyses (at least five recuts from the original block). Figure 1 shows a paradigmatic G1 HCC with an extralesional sample, which well represents the material under study.

18, 19 Therefore, we analyzed Lin−CD34+CD38−CD90+ cells in human adult livers and determined that this population represented 0.03%-0.05% of isolated single liver cells or CD45+ liver cells (Fig. 2). It is important to point out

that the Lin−CD34+CD38−CD90+ population is limited to its ability to generate lymphomyeloid engraftment with no T-cell engrafment;18 therefore, Gemcitabine nmr it does not represent multipotent HSCs. Because of the limitation of the size of adult donor livers (typically 2 × 106 total cells were isolated), it was not possible to purify Lin−CD34+CD38−CD90+ cells by FACS for biological study. Instead, we determined the methycellulose colony-forming ability of magnet-sorted Lin−CD34+ or Lin−CD45+ liver cell

populations. Indeed, 82% (18 of 22) of donor liver cell samples sorted into Lin−CD34+ and Lin−CD45+ populations were able to form colonies, including myeloid-lineage colonies (CFU-GM, CFU-G, and CFU-GM; Fig. 3) and erythroid-lineage colonies (BFU-E and CFU-E; Fig. 3). More convincingly, Lin−CD45+ or CD45+ liver cells from perfused learn more liver graft were able to repopulate

in NOD-SCID mice by detection of human CD45+ cells in the BM and blood of mice (Fig. 4A,B). These human CD45+ hematopoietic cells comprised ethrythoid and myeloid precursors and mature lymphocytes (Fig. 4C), although engraftment ability is low, ranging from 0.04% to 0.32% (Fig. 4C). Thus, by both hematopoietic methylcellulose colony formation and engraftment experiments, we are the first to convincingly demonstrate that HSPCs exist in human adult livers. It is known that marrow HSPCs are able to mobilize to the peripheral blood in response to cytotoxic agents and cytokines23 and can home directly to inflammation sites.23, 24 More interestingly, medchemexpress HSPCs can enter into the circulation, even in a steady state.23, 25 Here, we demonstrate the existence of HSPCs in human adult livers, although the capacity of CFU formation and hematopoietic-repopulating potential of liver HSPCs is relatively low. The important question is whether this very small population of HSPCs was mobilized from the BM during the transplantation process or if it persistently existed in the adult liver.

It is recommended for intermediate stage HCC (BCLC B). But there is no consensus concerning treatment modalities. Recently several prognostic scores have been proposed to guide the treatment decision: ART, HAP, ABCR (EASL 2014, abstract A-627-0008-01729). Purpose: To evaluate and compare these three prognostic scores on a multicenter independent cohort treated by TACE. Methods: This retrospective study included Child-Pugh A or B patients with BCLC B HCC, BCLC A HCC (not eligible for curative treatment) and

BCLC C HCC with limited portal vein thrombosis, treated ATR cancer by TACE from 01/2007 to 01/2013, without complementary treatment (RF or graft), not involved in the development of ABCR score. To compare the three scores, we used an independent cohort: 153 patients, median age 68 years, BCLC A 17%, BCLC B 69%, BCLC C 14% treated in Marseille and Nancy. Cirrhosis was viral 40%, related to alcohol 43%, to a fatty liver disease 12%. Median survival in the three scores, overall effect of find more scores on survival time (Wald test). Results: Patients in the independent cohort were treated an average of 2.75 TACE. The response rate (EASL criteria) was 61%. Median follow-up was 19 months [17–23]. HAP score

distinguished four groups: HAP A 31 months [25–37] vs. HAP B 31 months [20–51] vs. HAP C 22 months [17–25] vs. HAP D 18 months [6–32], p = 0.0454, but the risk of death in HAP B and D groups were not significantly different from the reference HAP A group (respectively HR 0.88 [0.52–1.50], p = 0.640, HR 1.56 [0.81–2.99],

p = 0.1820). ART score distinguished two groups with different survival: ART (0–1.5) 27 months [23–37] vs. ART (≥2.5) 19 months [14–25 ], p = 0.0013, but the risk of death of the ART 4 group was not significantly different from the reference ART 0 group (HR 1.61 [0.81–3.21], p = 0.178) conversely ART 1 group (HR 3.26 [1.91–5.55], p < .0001). The ABCR score distinguished three groups with different survival: ABCR ≤ 0: 37 months [27–49] vs. ABCR [1–3]: medchemexpress 17 months [14–20] vs. ABCR ≥ 4: 8 months [6–18], p < 0.0001 . The risk of death of ABCR [1–3] and ABCR ≥ 4 groups was significantly increased compared to the reference ABCR ≤ 0 group (respectively HR 3.85 [2.46–6.02], p < .0001, HR 14.72 [6.57–33], p < .0001). Conclusion: In this multicenter mainly BCLC B HCC series, the distribution of patients according to the ART and HAP scores is inaccurate because it is not correlated with prognosis. The ABCR score better distributes unresectable HCC and therefore optimize treatment: continuation of TACE, systemic therapy or therapeutic trial. Key Word(s): 1.

It is the suppressed expression of Ku70/80 leading to a persistent DNA damage and ROS/endoplasmic reticulum stress in TLR4mut liver.36 Indeed, isotopic expression of DNA

repair protein Ku70 can reverse the TLR4 mutation-enhanced susceptibility to the DEN-induced HCC through restoring the cellular senescence and activating autophagic flux in TLR4mut liver tissue. Thus, these results place TLR4 activity in the intersection of DNA damage/genome instability and senescence/autophagy/DNA repairing (Fig. 7F). The residual hepatic cells or the liver-infiltrating immune cells have been reported selleck to be involved in the pathogenesis of HCC development.31, 37 Indeed, microbial infection in the liver may recruit Alectinib a larger number of immune cells to the liver, and the infiltrated immune cells and secreted soluble factors play a critical role in the promotion of HCC development.10 However, if HCC is primarily caused by chemical agents or metabolic stresses, the residue liver cells undergoing premature senescence are predominant party to initiate and sustain inflammation participating in the regulation of HCC development.5 Obviously, the immunity against tumorigenesis is constituted by both liver-infiltrating

immune cells and residual hepatic cells. Interestingly, in addition to its expression in immune cells, functional TLR4 is also expressed by residual hepatic cells and the TLR4-mediated responses can therefore be derived from the activated residual hepatic cells or from the liver-infiltrating immune cells. In our current work, however, a failure of cellular senescence induction in the residual hepatic cells is more likely to link to loss of TLR4-mediated immunity, enhancing susceptibility to DEN-induced hepatocellular carcinogenesis and progression. This observation is supported by the fact that the filtration of macrophages was decreased and the wide-spectrum MCE公司 inflammatory response was

suppressed in the TLR4mut liver tissue; in addition, DNA damage, genomic instability, and malignant transformation were caused by DEN, a hepatic- but not immune-specific oncotoxic agent and a major trigger of senescent response. Thus, our study demonstrates a critical protection role of TLR4 against tumorigenesis and may help to develop new prophylactic and treatment approaches for HCC. The defects in DNA damage repair leading to genome instability is the hallmark of cancer, including HCC.38 Indeed, HCC is commonly secondary to cirrhosis following chronic microbe infection, genotoxic agents, and metabolic stress, which is often associated with genotoxic DNA damage and mutations of known DNA repair genes.39 For instance, the DNA repair complex and its regulatory proteins may critically influence vital cellular processes such as programmed cell death, cell proliferation, and inflammation, and thereby may play a critical role in the pathogenesis of human cancer.

In the 20% and 40% prevalence IDU treatment scenarios, total costs are lower than in the ex/non-IDU scenario because of reductions in onward infections (leading to higher QALYs and reduced HCV-associated medical costs). The lower the baseline prevalence, the higher the QALY gain when treating IDUs, as treatments result

in a larger relative reduction in prevalence. In the 60% prevalence setting, costs are higher for treating IDU than ex/non-IDU; any beneficial prevention effects are offset by increased reinfection. The ANCOVA analysis in Supporting Fig. 5 shows that most variability (55%) in the ICER at 40% prevalence results from uncertainty in the cost parameters associated with care in the different HCV progression states. Additional variability is related to uncertainty in the mild SVR utility value (6%) and the transition probabilities from mild to moderate (6%), moderate to PD98059 cirrhosis (12%), cirrhosis to decompensated cirrhosis (5%), and IDU death (7%). Uncertainty in the uninfected IDU utility value and costs related to antiviral treatment contributes little to the variability in projections. Figure 4 shows that none of the univariate sensitivity analyses

on the ICER (treatment of IDUs as compared with no treatment) for the 40% prevalence scenario changed the optimal policy choice of treating IDU. Reducing the SVR among IDUs by one-quarter or half increases the ICER by nearly 50% and 150%, respectively. Treatment of an all genotype 1 population results in a higher ICER (+50%) due to a lower SVR, whereas treating all genotype 2/3 reduces the ICER (−60%). SCH772984 concentration Lowering the uninfected ex-IDU utility value (to 0.9) and average lifespan by 7 years results in an increase in ICER (+40%) for treating IDUs and MCE公司 the ICER for treating

ex-IDUs also increases. Using a health discount rate of 0% instead of 3.5% per year substantially reduces the ICER to just below zero (cost saving) due to increased savings from future infections averted. Treatment at a moderate stage is more cost-effective than treating at a mild stage, with an ICER of £1,082. Increasing the time horizon to 100 years reduces the ICER by nearly 50% due to further prevention and treatment benefits, with reductions stabilizing at 200 years due to discounting. The ICER for treatment of ex/non-IDUs as compared with no treatment stabilizes at about £4,200 for long time horizons. Changes in IDU treatment delivery costs, treatment rate, or treatment duration do not alter the ICER substantially. Our results suggest treating chronic HCV infection among injectors and ex- or noninjectors is cost-effective, but treating injectors may be more cost-effective when the chronic HCV prevalence among IDU is below 60% (about 80% antibody prevalence). In these scenarios, treating injectors results in more QALYs gained through the prevention of onward transmission than are lost from reinfection.

Results from previous studies suggesting that cholangiocyte undergo EMT are inconclusive because they entirely rely on double immunofluorescence staining for cholangiocyte markers and surrogate markers for mesenchymal cells including FSP-1.20–22 As pointed out above, it remains unknown if FSP-1-positive cells express collagen and therefore also contribute to the ECM-producing cells in vivo. Cell fate tracking for cholangiocytes has not been performed so far and genetic evidence that cholangiocytes lose their epithelial characteristics and acquire a mesenchymal phenotype check details and start to

synthesize ECM is therefore still missing. Our current study did not address the role of cholangiocytes in EMT. To analyze if hepatocyte-derived cells indeed contribute to ECM production in liver fibrosis, we utilized a reporter mouse in which GFP is expressed under the murine collagen α1(I) promoter/enhancer in combination with a cell fate tracing technique used

in the previous study by Zeisberg et al.6 Our in vitro results using primary cultured hepatocytes initially appeared to support the concept of EMT. Hepatocytes not only exhibited fibroblast-like morphological changes, but also expressed collagen α1(I) in response to TGFβ-1. Cell fate tracing technique using ROSA26 stop β-gal and Alb Cre mice excluded the possibility that GFP-expressing cells were contaminating mesenchymal cells. However, the GFP-expressing hepatocytes did not express mesenchymal markers such as FSP-1 or α-SMA. A small number of cells that became positive for FSP-1 or α-SMA in hepatocyte culture click here were not positive for β-gal and were rare contaminating MCE公司 cells. Thus, our observation that hepatocytes express collagen α1(I) with a “fibroblast-like” morphological change does not satisfy the definition of EMT, as it

is not associated with mesenchymal marker expression. A number of studies have demonstrated that cultured hepatocytes express mesenchymal markers in response to TGFβ-1.13, 23 However, these studies failed to show that cells positive for mesenchymal markers were truly hepatocyte-derived cells and do not represent contaminating cells. Only Zeisberg et al.6 employed the cell fate tracing technique to demonstrate that hepatocyte-derived cells express a mesenchymal marker (FSP-1). The reliability of the immunostaining (FSP-1 and β-gal) is open to question (discussed below). The fact that we (Supporting Fig. S7) as well as Kaimori et al.13 observed no increase in FSP-1 mRNA levels in hepatocytes treated with TGFβ-1 challenges the observation of Zeisberg et al. Taken together, our study and previous reports do not provide evidence that primary cultured hepatocytes undergo EMT and acquire expression of FSP-1. More important, our in vivo experiments detected no hepatocyte-derived collagen type I-expressing cells.