Studies in nonhuman primates have been of major importance for experimental studies of human hepatitis viruses, including analyses of hepatitis A virus in New World monkeys (tamarins and owl monkeys), HBV, hepatitis D virus, and hepatitis C virus (HCV) in hominoids (chimpanzees), and hepatitis E virus in Old World monkeys (cynomolgus and rhesus macaques).[2-5] Chimpanzees are the only animal Gefitinib clinical trial model for studies of human HBV and HCV infections and related innate and adaptive host immune responses.[6] Chimpanzees have been available primarily for research in the United States, where several animal facilities

can perform studies in a suitable environment. However, a report from the Institute of Medicine (released December 15, 2011), evaluating the role of this model in biomedical research, has limited or eliminated most experimental research in chimpanzees funded by the National Institutes of Health, a major funding agency for such research.[7] The use of www.selleckchem.com/products/NVP-AUY922.html chimpanzees for persistent HBV was already rather limited because the chronicity rate in experimental infections is low, and only a small number of animals have been available. Cost has been another limiting factor. However, a recent study by Lanford

et al. showed how the chimpanzee model could be used to determine the effect of molecules affecting pathways of the immune system; it was demonstrated that a Toll-like receptor 7 agonist could effectively lower HBV viral load partly by inducing antigen-specific T- and natural killer cell responses.[8] New World monkeys (e.g., tamarins, marmosets, and owl and spider monkeys commonly used in biomedical research) do not appear to be susceptible

to human HBV. An HBV variant was identified in Woolly monkeys (endangered species) and could lead to acute, but not persistent, experimental infection in Spider monkeys.[9, 10] Among Old World selleck compound monkeys, there is evidence of occult human HBV infection of subgenotype A2 in baboons with detection of the HBV DNA genome at low titers in serum, but not the HBV surface antigen (HBsAg).[11] However, HBV could be transmitted to naïve baboons and HBV DNA could be detected for at least 6 months. It remains to be determined whether this will be a relevant model for studying chronic HBV infection. Cynomolgus and rhesus macaques are frequently used in biomedical research, but it has been unclear whether human HBV could be transmitted to these animals. The possibility of using rhesus monkeys for experimental human HBV infection was examined early after the discovery of HBV. Thus, in 1972, London et al. reported that HBV could be transmitted to rhesus monkeys (Macaca mulatta) and serially passaged to naïve monkeys, but this could not be confirmed subsequently.[12] In 2002, Gheit et al. reported that Barbary apes (M.

Studies in nonhuman primates have been of major importance for experimental studies of human hepatitis viruses, including analyses of hepatitis A virus in New World monkeys (tamarins and owl monkeys), HBV, hepatitis D virus, and hepatitis C virus (HCV) in hominoids (chimpanzees), and hepatitis E virus in Old World monkeys (cynomolgus and rhesus macaques).[2-5] Chimpanzees are the only animal PLX3397 manufacturer model for studies of human HBV and HCV infections and related innate and adaptive host immune responses.[6] Chimpanzees have been available primarily for research in the United States, where several animal facilities

can perform studies in a suitable environment. However, a report from the Institute of Medicine (released December 15, 2011), evaluating the role of this model in biomedical research, has limited or eliminated most experimental research in chimpanzees funded by the National Institutes of Health, a major funding agency for such research.[7] The use of Navitoclax in vivo chimpanzees for persistent HBV was already rather limited because the chronicity rate in experimental infections is low, and only a small number of animals have been available. Cost has been another limiting factor. However, a recent study by Lanford

et al. showed how the chimpanzee model could be used to determine the effect of molecules affecting pathways of the immune system; it was demonstrated that a Toll-like receptor 7 agonist could effectively lower HBV viral load partly by inducing antigen-specific T- and natural killer cell responses.[8] New World monkeys (e.g., tamarins, marmosets, and owl and spider monkeys commonly used in biomedical research) do not appear to be susceptible

to human HBV. An HBV variant was identified in Woolly monkeys (endangered species) and could lead to acute, but not persistent, experimental infection in Spider monkeys.[9, 10] Among Old World selleckchem monkeys, there is evidence of occult human HBV infection of subgenotype A2 in baboons with detection of the HBV DNA genome at low titers in serum, but not the HBV surface antigen (HBsAg).[11] However, HBV could be transmitted to naïve baboons and HBV DNA could be detected for at least 6 months. It remains to be determined whether this will be a relevant model for studying chronic HBV infection. Cynomolgus and rhesus macaques are frequently used in biomedical research, but it has been unclear whether human HBV could be transmitted to these animals. The possibility of using rhesus monkeys for experimental human HBV infection was examined early after the discovery of HBV. Thus, in 1972, London et al. reported that HBV could be transmitted to rhesus monkeys (Macaca mulatta) and serially passaged to naïve monkeys, but this could not be confirmed subsequently.[12] In 2002, Gheit et al. reported that Barbary apes (M.

0%, 45.6%, and 20.4%, respectively, and GPX1; 67.0%, 31.1%, and 1.9%, respectively) and the larger control group matched for sex and age. Genotype distribution of SOD2 and GPX1 in the main pharmacological drug groups

related to DILI is outlined in Table 2. Subjects with an SOD2 Ala allele (Val/Ala or Ala/Ala genotype) had a higher risk of DILI than those with the SOD2 Val/Val genotype, both in overall drugs studied (n = 185; OR = 1.7 [1.1-2.6], Pc = 0.048) and in the CNS drugs category (n = 28; OR = 3.8 [1.1-13.0], P = 0.029/Pc = 0.058). When the analysis of the SOD2 polymorphism was restricted to patients with cholestatic/mixed liver injury, the SOD2 C allele frequency was higher among patients receiving NSAIDs (n = 12; OR = 2.2 [1.2-3.8], Pc = 0.017) and CNS drugs

(n = 12; OR = 3.1 [1.7-5.6], Pc = 0.0003). this website Whereas the GPX1 T (Leu) allele was more frequently found in DILI patients induced by anti-infective drugs (n = 35; OR = 2.6 [1.3-4.9], Pc = 0.011). On the genotype level, the frequency of overall DILI patients carrying the GPX1 TC and TT genotypes was higher than that in the control subjects (n = 185; OR = 1.5 [1.0-2.2], P = 0.042/Pc = 0.084) and in the group receiving anti-infective drugs (n = 59; OR = 2.3 [1.3-4.1], Pc = 0.0098). To justify the use of the larger non–drug-matched Ceritinib datasheet control group, analyses were also undertaken using smaller drug-matched control groups. An association between the SOD2 C allele and cholestatic/mixed type of liver injury induced by NSAIDs was found when using the drug-matched control group (OR = 2.6 [1.4-4.5], Pc = 0.0028). In addition, no association was found between the SOD2 C allele and cholestatic/mixed type of liver injury induced by amoxicillin-clavulanate when compared with drug-matched controls, reflecting the results obtained with the larger sex- and age-matched control group. Moreover, the GPX1 allele frequency in NSAID-matched and amoxicillin-clavulanate–matched

controls corresponded to those of the larger sex- and age-matched control group (Supporting Information Table 1). The SOD2 Ala/Ala genotype distribution in DILI selleckchem patients classified by the formation of reactive intermediates and according to the type of liver injury is outlined in Table 3. Patients with cholestatic/mixed type of DILI induced by quinones, quinone-like intermediates (quinone methides and quinone imines), or epoxides (n = 58) were found to be more prone to contain the SOD2 Ala/Ala genotype when compared with healthy controls (OR = 3.0 [1.7-5.5], Pc = 0.0008). Similarly, a positive association between the SOD2 Ala/Ala genotype and the risk of cholestatic/mixed type of DILI from drugs forming S-oxides, diazenes, nitroanion radicals, and iminium ions (n = 5) was observed (OR = 16.0 [1.8-146.1], Pc = 0.009).

Disclosures: Marcus Dorner – Grant/Research Support: CN Bio Innovations, Ltd The following people have nothing to disclose: Eva Billerbeck, Michiel C. Mom-mersteeg, Amir Shlomai, Jing W. Xiao, Linda Andrus, Ankit

Bhatta, Anuradha Krishnan, Michael Charlton, Luis Chiriboga, Charles M. Rice, Ype P. De Jong Covalently closed circular DNA (ccc-DNA) of hepatitis B virus (HBV) acts as a reservoir for reactivation of viral replication and whose quantification can be used as a marker of persistent intracellular replication. The determinants of intracellular levels of replication have rarely been evaluated in HBV-human immunodeficiency virus (HIV) co-infected patients. Sixty HIV-HBV co-infected patients PCI-32765 chemical structure with at least one liver biopsy during follow-up in the French HIV-HBV cohort were included. HBV ccc-DNA and total intracellular HBV-DNA were extracted from biopsies and quantified by real-time PCR. Risk-factors of intra-cellular replication were determined using mixed-effect linear regression models. At the time of biopsy, 35 (61.4%) patients were HBeAg-positive and 23 (46.9%) had detectable serum HBV-DNA (median: 3.10 log10 IU/mL, IQR:2.75-5.38). Among the 22 patients undergoing tenofovir (TDF)-containing antiretroviral therapy, cumulative

TDF-duration was at a median 17.8 months (IQR:5.7-31.0). Overall, median HBV ccc-DNA was -1.10 log10 copies/cell (IQR:-1.70, check details -0.29) and total intra-cellular HBV-DNA was 0.27 log10 copies/cell (IQR:-0.39, 2.00). In multivariable analysis, patients with HBeAg-posi-tive serology had significantly higher levels of HBV ccc-DNA

(+0.76 log10 copies/mL; 95%CI:0.39, 1.13; p<0.001), whereas those with a nadir CD4+ cell count above 250/mm3 had significantly lower HBV ccc-DNA levels (-0.57 log10 learn more copies/mL; 95%CI:-0.95, -0.19; p=0.004). Furthermore, patients with longer than 3 years of cumulative TDF-duration had significantly lower HBV ccc-DNA levels after adjustment (-0.88 log10 copies/cell: 95%CI:-1.40, -0.35; p=0.001). Accordingly, when focusing on patients undergoing TDF with a biopsy at TDF-initiation and sometime during therapy (median duration: 35.3 months, range: 20.2-56.6), most exhibited strong declines in HBV ccc-DNA (median change in log10 copies/ cell/year:-0.46, range:-0.67, 0; n=7). HBV ccc-DNA levels did remain detectable at the end of follow-up for all patients, yet at very low levels (median: 0.04 copies/cell, range: 0.01, 0.31). The results above were similar when using total intracellular HBV-DNA levels as an end-point. In conclusion, severe immu-nosuppression is associated with intracellular HBV replication in coinfected patients. Treatment with TDF is linked to large declines in ccc-DNA, yet replication within the hepatocyte still persists after long periods of treatment.

Nonetheless, it provides an important step forward in addressing this potentially important issue in a large, well-characterized cohort of patients and will hopefully Small molecule library solubility dmso engender additional interest and research in this area. Taken together, the results from both studies also highlight the insensitivity of current highly sensitive methods of serum HBV DNA testing for the detection of OBI and the importance

of studies of HBV infection and replication in liver tissue samples for understanding the true prevalence and clinical relevance of OBI. In conclusion, to achieve a clear understanding of the role of OBI in buy AG-014699 the development of chronic liver disease and HCC, robust answers to the following research questions are needed. Is there a difference between OBI detected in low-prevalence versus high-prevalence HBV endemic regions? Do the samples and methods used for detecting OBI have adequate

sensitivity, specificity, and precision? Are the study designs free from unintended bias? Additional cohort, case-control, and population-based studies should shed additional light on the role of OBI in development of HCC in chronic HCV patients and those with cryptogenic liver disease and are urgently needed. These investigations will hopefully determine whether OBI is truly a significant, important

risk factor for advanced liver disease and HCC and what interventions, if any, are needed to mitigate selleck products this risk. “
“Fasudil, a Rho-kinase inhibitor, has been shown to reduce portal venous pressure in cirrhotic rats. However, its effects on portal and systemic hemodynamics have not been investigated in cirrhotic patients with portal hypertension. The aim of this study was to assess the effects of fasudil on the portal and systemic hemodynamics of cirrhotic patients with portal hypertension. Twenty-three patients with cirrhosis and portal hypertension were studied. Systemic and portal hemodynamics were measured prior to and 50 min after the initiation of intravenous administration of 30 mg fasudil (n = 15) or placebo (n = 8). After fasudil, there were significant decreases in both mean arterial pressure (P < 0.05) and systemic vascular resistance (P < 0.05), whereas the heart rate increased significantly (P < 0.05). There was a significant decrease in the hepatic venous pressure gradient (P < 0.05). Portal vascular resistance also decreased significantly (P < 0.01). Placebo caused no significant effects. There were no symptomatic reactions caused by changes in the mean arterial pressure or heart rate after fasudil.

Nonetheless, it provides an important step forward in addressing this potentially important issue in a large, well-characterized cohort of patients and will hopefully http://www.selleckchem.com/products/VX-809.html engender additional interest and research in this area. Taken together, the results from both studies also highlight the insensitivity of current highly sensitive methods of serum HBV DNA testing for the detection of OBI and the importance

of studies of HBV infection and replication in liver tissue samples for understanding the true prevalence and clinical relevance of OBI. In conclusion, to achieve a clear understanding of the role of OBI in Ibrutinib the development of chronic liver disease and HCC, robust answers to the following research questions are needed. Is there a difference between OBI detected in low-prevalence versus high-prevalence HBV endemic regions? Do the samples and methods used for detecting OBI have adequate

sensitivity, specificity, and precision? Are the study designs free from unintended bias? Additional cohort, case-control, and population-based studies should shed additional light on the role of OBI in development of HCC in chronic HCV patients and those with cryptogenic liver disease and are urgently needed. These investigations will hopefully determine whether OBI is truly a significant, important

risk factor for advanced liver disease and HCC and what interventions, if any, are needed to mitigate check details this risk. “
“Fasudil, a Rho-kinase inhibitor, has been shown to reduce portal venous pressure in cirrhotic rats. However, its effects on portal and systemic hemodynamics have not been investigated in cirrhotic patients with portal hypertension. The aim of this study was to assess the effects of fasudil on the portal and systemic hemodynamics of cirrhotic patients with portal hypertension. Twenty-three patients with cirrhosis and portal hypertension were studied. Systemic and portal hemodynamics were measured prior to and 50 min after the initiation of intravenous administration of 30 mg fasudil (n = 15) or placebo (n = 8). After fasudil, there were significant decreases in both mean arterial pressure (P < 0.05) and systemic vascular resistance (P < 0.05), whereas the heart rate increased significantly (P < 0.05). There was a significant decrease in the hepatic venous pressure gradient (P < 0.05). Portal vascular resistance also decreased significantly (P < 0.01). Placebo caused no significant effects. There were no symptomatic reactions caused by changes in the mean arterial pressure or heart rate after fasudil.

9%). Hepatitis C was the cause of cirrhosis in 40.8% of the patients, alcohol abuse in

17.5% selleck chemicals and hepatitis B in 3.9%. The mean MELD score was 15.7 ± 6.1 and 36.9% of the individuals were Child-Pugh C. IGF-1 levels positively correlated with albumin levels and negatively correlated with INR, CPR, total bilirubin and MELD. Significantly lower IGF-1 levels were observed in Child-Pugh C patients (P = 0.007) but not in subjects with ACLF (P = 0.222). The 90-day mortality was 26.2% and it was associated in the bivariate analysis with older age, bacterial infection, presence of ascites, hepatic encephalop-athy, Child-Pugh C and ACLF at admission. Concerning laboratory data, 90-day mortality was associated with higher creatinine, INR, CRP, venous lactate, total bilirubin, MELD and lower sodium, albumin and IFG-1 at admission. Stepwise forward logistic regression analysis including variables with P < 0.01 in the bivariate analysis showed that MELD score (OR 1.20, 95% CI 1.08-1.34, P = 0.001), ascites at admission (OR 12.37, 95% CI 2.73-55.96, P = 0.001) and IGF-1 levels (OR 0.91, 95% CI 0.84-0.99, P = 0.031) were independently associated with 90-day mortality. The Kaplan-Meier survival probability (figure) at 90-day was 87.8% in patients with IGF-1 > 10 ng/mL and 61.1% for subjects www.selleckchem.com/products/cb-839.html with IGF-1 < 10 ng/mL (P

= 0.003). Significantly lower IGF-1 levels were found at the time of acute decompensation

of cirrhosis as compared to the outpatient evaluation (21.9 ± 23.3 ng/mL vs. 49.3 ± 33.3 ng/mL, P < 0.001). Conclusion: IGF-1 levels decrease during acute decompensation of cirrhosis and were independently associated with short-term prognosis. Disclosures: The following people have nothing to disclose: Bruno S. Colombo, Marcelo F. Ronsoni, Pedro E. Soares selleck screening library e Silva, Leonardo Fayad, Leticia M. Wildner, Maria Luiza Bazzo, Esther B. Dantas-Correa, Janaina L. Narciso-Schiavon, Leonardo L. Schiavon Patients with end-stage liver disease candidates for liver transplantation are sorted according to MELD score. The Systemic Inflammatory Response Syndrome impacts on the prognosis of these patients but is not taken into account by the MELD. In a recent study CRP a marker of systemic inflammation, has been reported to predict 6-month mortality in hospitalized cirrhotic patients with Child-Pugh score>B7. This study demonstrated the good prognostic value of a 3-variables model incorporating MELD score, extrahepatic comorbidities, and variation of CRP levels within 15 days. Objectives: 1) to provide an external validation of the pejorative influence of sustained high CRP levels in cirrhotic patients;2) to optimize the prognostic model without considering extrahepatic comorbidities to make it more appropriate to the context of liver transplantation, 3) to test the model for predicting 3 month mortality.

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 ��-catenin signaling 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 Rucaparib in vivo were not positive for β-gal and were rare contaminating this website 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.

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 BGJ398 order 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 Z-VAD-FMK clinical trial were not positive for β-gal and were rare contaminating selleck chemicals 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.

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 HSP inhibitor 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 see more were not positive for β-gal and were rare contaminating selleckchem 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.