1-3 Knowledge of the oncogenic processes and the signaling pathways regulating HCC cell proliferation, survival, invasion, and metastasis has led to the development of targeted therapies with positive results, as exemplified by the multitarget inhibitor, sorafenib.2 However, notwithstanding the survival

benefits of sorafenib, there is still room for improvement, and current research is aiming to combine molecular therapies. To this end, increasing knowledge on the signaling pathways critical for HCC progression is of crucial importance. Connective tissue growth factor (CTGF) is a cysteine-rich secreted protein that interacts with a variety Buparlisib research buy of extracellular matrix components and cell-surface proteins, such as fibronectin, proteoglycans, and integrins, strongly influencing cellular behavior.4 CTGF participates in many biological processes, including cell proliferation, survival, migration, angiogenesis, wound healing, and cancer development.4-6 In the liver, CTGF has been recognized as a key profibrogenic factor, its expression is increased in fibrotic human and rat liver, and the manipulation of CTGF levels in experimental FK228 concentration fibrosis modulates the course of the disease.6 More recently, CTGF expression was reported

to be elevated in HCC tissues, and HCC patients with high serum CTGF levels show reduced survival, attesting to the potential relevance of CTGF in HCC progression.7, 8 Transforming growth factor beta (TGF-β) is

regarded as the major inducer of CTGF expression, and evidence suggests that CTGF, indeed, mediates many of the pathological effects of TGF-β in liver disease, including fibrosis development and HCC progression.4, 9 In view of all buy ZD1839 this, the understanding of CTGF regulation and biological effects in liver cancer cells would be important for the characterization of this factor as a molecular target in HCC. Previously, we demonstrated that CTGF expression in experimental liver fibrosis was affected by the epidermal growth factor receptor (EGFR) ligand, amphiregulin (AR), and that AR directly promoted CTGF expression in human and mouse fibrogenic cells.10 Signaling through the EGFR is regarded as an important mechanism in hepatocarcinogenesis and as a target for molecular therapies.2, 3, 11 Here, we demonstrate that CTGF expression in HCC cells participates in cell proliferation, survival, and inflammatory gene expression and is regulated by EGFR activation in a novel cross-talk with the oncogenic transcriptional coactivator, Yes-associated protein (YAP).

To identify the resistance gene(s) against stripe rust, Zhongliang 12 was crossed with stripe rust susceptible genotype Mingxian 169, and F1, F2, F2 : 3 and BC1 progenies were

tested with Chinese Pst race CYR30 and CYR31 in seedling stage in greenhouse. Zhongliang 12 possessed different dominant genes www.selleckchem.com/products/pexidartinib-plx3397.html for resistance to each race. Linkage maps were constructed with four simple sequence repeats (SSRs) markers, Xwmc695, Xcfd20, Xbarc121 and Xbarc49, for the gene on wheat chromosome 7AL conferring resistance to CYR30 (temporarily designated as Yrzhong12-1) with genetic distance ranging from 3.1 to 10.8 cM and four SSR markers, Xpsp3003, Xcfd2129, Xwmc673 and Xwmc51, for the gene on wheat chromosome 1AL conferring resistance to CYR31 (temporarily designated as Yrzhong12-2) with genetic distance ranging from 3.9 cM to 9.3 cM. The molecular markers closely linked to each gene should be useful

in marker-assisted selection in breeding programmes for against stripe rust. “
“In the present study, the mechanism of resistance to Plasmopara halstedii, the downy mildew pathogen of sunflower, triggered by three resistance-inducing chemicals, benzo (1,2,3) thiadiazole-7-carbothioic acid S-methyl ester (BTH), DL-β-amino butyric acid (BABA) and 2,6-dichloroisonicotinic acid (INA), was investigated in susceptible, www.selleckchem.com/products/cx-4945-silmitasertib.html completely resistant and partially resistant sunflower genotypes. By applying P. halstedii-specific primers, no detectable pathogen marker transcript accumulation was found in the infected but completely resistant sunflower hypocotyls; however, pretreatments with either of the three resistance inducers decreased the transcript accumulation in both the infected susceptible and the partially resistant lines. Benzothiadiazole pretreatment before inoculation considerably enhanced enzyme activities in the infected susceptible and the completely resistant genotypes but not find more in partially resistant plants. Pretreatment with resistance inducers before inoculation increased glutathione S-transferase, defensin and catalase transcript levels in the susceptible but decreased in the partially

resistant plants. Our results indicate that the resistance-inducing chemicals can improve resistance in all of the sunflower genotypes to downy mildew and increase enzyme activities of peroxidase and polyphenol oxidase, as well as accumulation of mRNAs of glutathione S-transferase, defensin and catalase. However, it is important to emphasize that activation of these defence-related proteins did not correlate with the degree of resistance, but rather with the amount of necrotic tissues. “
“Surveys were made in the main grape growing region (Southeast Anatolia) of Turkey for the occurrence of Grapevine leafroll-associated virus-5 (GLRaV-5). Plant samples with typical leafroll symptoms and mealybugs, Planococcus ficus (Signoret) were used for assessing the occurrence of GLRaV-5 by RT-PCR.

9, 17 Our novel finding on the reduced MAVS oligomerization is in accordance with the impaired function of the helicase receptor-MAVS signaling pathway. Mitochondrial dysfunction is a key component of fat accumulation, ROS generation, and the progression of inflammation in NASH.18 Thus, it is plausible that translocation of MAVS from the mitochondria to the cytosol could

be a consequence of mitochondrial damage in steatohepatitis. In addition to MAVS redistribution, we found other indications of mitochondrial damage, such as cytochrome c leak AZD3965 mouse from the mitochondria to cytoplasm, enrichment of mitochondria with β-actin, and increased activation of cellular damage pathways. Translocation of β-actin to the mitochondria leading to disruption of mitochondrial membrane was shown in influenza virus–stimulated macrophages.30 We found markedly elevated β-actin protein levels in mitochondrial fractions in steatohepatitis providing evidence

for mitochondrial damage in NASH. In normal hepatocytes, MAVS is localized in the outer mitochondrial membrane.9 Our novel data indicate increased activation of multiple caspases, including caspase 1 and caspase 8, in MCD diet–induced steatohepatitis, suggesting a possible link between MAVS cleavage and caspase activation. Several viruses, including hepatitis C (NS3/4A protease) and hepatitis A (3ABC protease), disrupt the host antiviral response by cleaving MAVS from mitochondria.20, 21 An apoptotic cleavage of MAVS has also been described.21 In NASH, both the death receptor–induced

GDC-0199 supplier and cellular stress–induced apoptotic pathways are involved, and apoptosis is indicated by increased caspase 3 activity and plasma cytokeratin 18 fragments.31, 32 Studies have shown that the pan-caspase inhibitor carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone prevents the cleavage of MAVS, whereas selective blockade of caspase 8, 9, or 3 was not sufficient to prevent MAVS cleavage.21 Relevant to our data, the pan-caspase inhibitor blocks both apoptotic caspases and caspase 1.21, 22 Thus, MAVS cleavage from the mitochondria in NASH is likely to be related to the increased caspase 8 and caspase 1 observed in our experiments. Damaged proteins are degraded Succinyl-CoA by proteasomes in the cytoplasm or nucleus.33 We show for the first time that MAVS protein preferentially binds to the proteasomal protein PSMA7 in fatty livers, suggesting that the damaged, cleaved MAVS protein from the mitochondria accumulates in the cytoplasm and is likely degraded by the proteasomes. Virus-induced apoptosis requires MAVS in primary mouse fibroblasts25 and MAVS itself can induce caspase-dependent apoptosis. It has been shown that poly(I:C) initiates apoptosis through MAVS.34 However, MAVS levels were decreased in MCD diet–induced steatohepatitis in our experiments.

Moreover, long-term studies of dieting indicate that the majority of individuals who dieted regain virtually all of the weight that was lost after dieting, regardless of whether they maintain their diet or exercise program.[8-10] Therefore, the maintenance of weight loss is still one of the biggest challenges of dietary interventions in patients with NAFLD. Provide 200–800 calories SAHA HDAC clinical trial per day, maintaining protein intake but limiting calories from both fat and carbohydrates. Must be undertaken with medical supervision to prevent adverse side-effects, such as loss

of lean muscle mass, increased risks of gout, gallbladder stone, and electrolyte imbalances. Aside from the possibility of achieving weight loss through caloric restriction (either low in carbohydrates or low in fats) as GSK458 a treatment for NAFLD, many dietary factors (especially macronutrients) can directly influence the development of NAFLD (Table 2).[3-7, 12-27] Manipulation of dietary composition might affect the outcomes of NAFLD and associated metabolic disorders independent of weight loss.[4-6] The dietary carbohydrates are often divided into complex carbohydrate (refer to any sort of digestible saccharide present in a whole food, where fiber, vitamins, and minerals are also found), or simple carbohydrates such as monosaccharides and disaccharides

(refer to sugar, provide calories but few other nutrients, and raise blood glucose rapidly especially if processed). Dietary carbohydrate

especially sugars contribute to increased circulating insulin and triglyceride concentrations and lead to increased hepatic de novo lipogenesis and decreased hepatic insulin sensitivity Celecoxib because of the lipogenic potential of fructose during liver metabolism.[12-16] In addition, recent genome-wide studies have identified several polymorphisms that contribute to increased liver fat accumulation, with some of these genes relating to dietary carbohydrate and sugar consumption.[7, 33] Dietary fructose consumption primarily in the form of soft drinks worldwide has increased in parallel with the increase in obesity, diabetes, and NAFLD, and some studies have suggested a direct association.[1-6] The role of fructose and sucrose in NAFLD and metabolic disorders has been thoroughly reviewed elsewhere. Low-carbohydrate diets are increasingly employed for treatment of obesity and NAFLD; they have been shown to promote weight loss, decrease intrahepatic triglyceride content, and improve metabolic parameters of patients with obesity.[4-6, 9, 34] However, the relationship between long-term maintenance on low-carbohydrate diets and systemic insulin resistance in humans remains to be elucidated. In addition, low glycemic index (GI ≤ 55) foods such as oats have been shown to increase appetite, reduce calories intake, and decrease plasma glucose and total cholesterol levels.

Moreover, long-term studies of dieting indicate that the majority of individuals who dieted regain virtually all of the weight that was lost after dieting, regardless of whether they maintain their diet or exercise program.[8-10] Therefore, the maintenance of weight loss is still one of the biggest challenges of dietary interventions in patients with NAFLD. Provide 200–800 calories http://www.selleckchem.com/products/ly2835219.html per day, maintaining protein intake but limiting calories from both fat and carbohydrates. Must be undertaken with medical supervision to prevent adverse side-effects, such as loss

of lean muscle mass, increased risks of gout, gallbladder stone, and electrolyte imbalances. Aside from the possibility of achieving weight loss through caloric restriction (either low in carbohydrates or low in fats) as selleck chemicals llc a treatment for NAFLD, many dietary factors (especially macronutrients) can directly influence the development of NAFLD (Table 2).[3-7, 12-27] Manipulation of dietary composition might affect the outcomes of NAFLD and associated metabolic disorders independent of weight loss.[4-6] The dietary carbohydrates are often divided into complex carbohydrate (refer to any sort of digestible saccharide present in a whole food, where fiber, vitamins, and minerals are also found), or simple carbohydrates such as monosaccharides and disaccharides

(refer to sugar, provide calories but few other nutrients, and raise blood glucose rapidly especially if processed). Dietary carbohydrate

especially sugars contribute to increased circulating insulin and triglyceride concentrations and lead to increased hepatic de novo lipogenesis and decreased hepatic insulin sensitivity Glutathione peroxidase because of the lipogenic potential of fructose during liver metabolism.[12-16] In addition, recent genome-wide studies have identified several polymorphisms that contribute to increased liver fat accumulation, with some of these genes relating to dietary carbohydrate and sugar consumption.[7, 33] Dietary fructose consumption primarily in the form of soft drinks worldwide has increased in parallel with the increase in obesity, diabetes, and NAFLD, and some studies have suggested a direct association.[1-6] The role of fructose and sucrose in NAFLD and metabolic disorders has been thoroughly reviewed elsewhere. Low-carbohydrate diets are increasingly employed for treatment of obesity and NAFLD; they have been shown to promote weight loss, decrease intrahepatic triglyceride content, and improve metabolic parameters of patients with obesity.[4-6, 9, 34] However, the relationship between long-term maintenance on low-carbohydrate diets and systemic insulin resistance in humans remains to be elucidated. In addition, low glycemic index (GI ≤ 55) foods such as oats have been shown to increase appetite, reduce calories intake, and decrease plasma glucose and total cholesterol levels.

Moreover, long-term studies of dieting indicate that the majority of individuals who dieted regain virtually all of the weight that was lost after dieting, regardless of whether they maintain their diet or exercise program.[8-10] Therefore, the maintenance of weight loss is still one of the biggest challenges of dietary interventions in patients with NAFLD. Provide 200–800 calories IWR-1 solubility dmso per day, maintaining protein intake but limiting calories from both fat and carbohydrates. Must be undertaken with medical supervision to prevent adverse side-effects, such as loss

of lean muscle mass, increased risks of gout, gallbladder stone, and electrolyte imbalances. Aside from the possibility of achieving weight loss through caloric restriction (either low in carbohydrates or low in fats) as NVP-LDE225 nmr a treatment for NAFLD, many dietary factors (especially macronutrients) can directly influence the development of NAFLD (Table 2).[3-7, 12-27] Manipulation of dietary composition might affect the outcomes of NAFLD and associated metabolic disorders independent of weight loss.[4-6] The dietary carbohydrates are often divided into complex carbohydrate (refer to any sort of digestible saccharide present in a whole food, where fiber, vitamins, and minerals are also found), or simple carbohydrates such as monosaccharides and disaccharides

(refer to sugar, provide calories but few other nutrients, and raise blood glucose rapidly especially if processed). Dietary carbohydrate

especially sugars contribute to increased circulating insulin and triglyceride concentrations and lead to increased hepatic de novo lipogenesis and decreased hepatic insulin sensitivity Sitaxentan because of the lipogenic potential of fructose during liver metabolism.[12-16] In addition, recent genome-wide studies have identified several polymorphisms that contribute to increased liver fat accumulation, with some of these genes relating to dietary carbohydrate and sugar consumption.[7, 33] Dietary fructose consumption primarily in the form of soft drinks worldwide has increased in parallel with the increase in obesity, diabetes, and NAFLD, and some studies have suggested a direct association.[1-6] The role of fructose and sucrose in NAFLD and metabolic disorders has been thoroughly reviewed elsewhere. Low-carbohydrate diets are increasingly employed for treatment of obesity and NAFLD; they have been shown to promote weight loss, decrease intrahepatic triglyceride content, and improve metabolic parameters of patients with obesity.[4-6, 9, 34] However, the relationship between long-term maintenance on low-carbohydrate diets and systemic insulin resistance in humans remains to be elucidated. In addition, low glycemic index (GI ≤ 55) foods such as oats have been shown to increase appetite, reduce calories intake, and decrease plasma glucose and total cholesterol levels.

A combination

algorithm was developed and validated prospectively in 170 CHC additional patients. Results:  Epithelial membrane antigen at 130 kDa was identified, purified and quantified in sera of CHC patients using ELISA. Based on these encouraging results, we purified and developed a direct ELISA for the quantitation of EMA in sera of CHC. MDA selected a score for the prediction of significant liver fibrosis patients based on measurements of EMA, aspartate aminotransferase to platelet ratio index and albumin. Areas under the ROC curves (AUC) of the score for the three biomarkers were 0.82 for patients with liver fibrosis (F1–F4), 0.86 for significant liver fibrosis (F2–F4), 0.87 for advanced liver fibrosis (F3–F4) and 0.86 for liver cirrhosis (F4). The results of the validation study PLX3397 price demonstrated that (74%) of patients could have avoided liver biopsy. Conclusion:  This score was validated for the prediction of liver fibrosis stages and may minimize the need for liver biopsy. “
“Aim:  To evaluate the efficacy of reduction therapy of natural human interferon (IFN)-β and ribavirin in elderly patients with hepatitis C virus (HCV) genotype 1b and high viral load who had complications of anemia, low bodyweight (<50 kg), diabetes mellitus and/or hypertension.

Methods:  selleck inhibitor Inclusion criteria were age of 65 years or older, HCV genotype 1b, and serum HCV RNA level of 5.0 logIU/mL or higher. A total of 23 subjects with hemoglobin level of less than 13 g/dL, low bodyweight, diabetes mellitus and/or hypertension were enrolled in this study (reduction-dose group). IFN-β was administrated i.v. at a dose of 6 million units daily for 4 weeks initially, followed by three times a week for 44 weeks. Ribavirin was given daily for 48 weeks at a decreased dose of one tablet per day compared to the ordinary dose described based on bodyweight. As a control, another 22 patients without anemia, low bodyweight and/or complications treated with the standard dose of ribavirin (standard-dose group) were enrolled. Results:  Patients’ rates with further dose reduction or

discontinuation of treatment was 26.1% (6/23) in the reduction-dose group and 77.3% (17/22) in the standard-dose group. The sustained virological response Glutamate dehydrogenase (SVR) was 39.1% (9/23) in the reduction-dose group and 27.3% (6/22) in the standard-dose group (P = 0.404). Based on genetic variations near the IL28B gene (rs8099917), SVR was 44.1% (15/34) in patients with TT and 0% (0/11) in patients with TG (P = 0.008). Conclusion:  The reduction therapy of IFN-β and ribavirin in elderly HCV patients with genotype 1b, high viral load, IL28B gene (rs8099917) of TT who had complications of anemia, low bodyweight, diabetes mellitus and/or hypertension is one possible selection of treatment. “
“Routine light microscopy identifies two distinct epithelial cell populations in normal human livers: hepatocytes and biliary epithelial cells (BECs).

A combination

algorithm was developed and validated prospectively in 170 CHC additional patients. Results:  Epithelial membrane antigen at 130 kDa was identified, purified and quantified in sera of CHC patients using ELISA. Based on these encouraging results, we purified and developed a direct ELISA for the quantitation of EMA in sera of CHC. MDA selected a score for the prediction of significant liver fibrosis patients based on measurements of EMA, aspartate aminotransferase to platelet ratio index and albumin. Areas under the ROC curves (AUC) of the score for the three biomarkers were 0.82 for patients with liver fibrosis (F1–F4), 0.86 for significant liver fibrosis (F2–F4), 0.87 for advanced liver fibrosis (F3–F4) and 0.86 for liver cirrhosis (F4). The results of the validation study Selleck AZD5363 demonstrated that (74%) of patients could have avoided liver biopsy. Conclusion:  This score was validated for the prediction of liver fibrosis stages and may minimize the need for liver biopsy. “
“Aim:  To evaluate the efficacy of reduction therapy of natural human interferon (IFN)-β and ribavirin in elderly patients with hepatitis C virus (HCV) genotype 1b and high viral load who had complications of anemia, low bodyweight (<50 kg), diabetes mellitus and/or hypertension.

Methods:  Osimertinib mouse Inclusion criteria were age of 65 years or older, HCV genotype 1b, and serum HCV RNA level of 5.0 logIU/mL or higher. A total of 23 subjects with hemoglobin level of less than 13 g/dL, low bodyweight, diabetes mellitus and/or hypertension were enrolled in this study (reduction-dose group). IFN-β was administrated i.v. at a dose of 6 million units daily for 4 weeks initially, followed by three times a week for 44 weeks. Ribavirin was given daily for 48 weeks at a decreased dose of one tablet per day compared to the ordinary dose described based on bodyweight. As a control, another 22 patients without anemia, low bodyweight and/or complications treated with the standard dose of ribavirin (standard-dose group) were enrolled. Results:  Patients’ rates with further dose reduction or

discontinuation of treatment was 26.1% (6/23) in the reduction-dose group and 77.3% (17/22) in the standard-dose group. The sustained virological response SPTLC1 (SVR) was 39.1% (9/23) in the reduction-dose group and 27.3% (6/22) in the standard-dose group (P = 0.404). Based on genetic variations near the IL28B gene (rs8099917), SVR was 44.1% (15/34) in patients with TT and 0% (0/11) in patients with TG (P = 0.008). Conclusion:  The reduction therapy of IFN-β and ribavirin in elderly HCV patients with genotype 1b, high viral load, IL28B gene (rs8099917) of TT who had complications of anemia, low bodyweight, diabetes mellitus and/or hypertension is one possible selection of treatment. “
“Routine light microscopy identifies two distinct epithelial cell populations in normal human livers: hepatocytes and biliary epithelial cells (BECs).

This distinguishes this signature with regard to long-term outcome, compared to the clinical situation early post-OLT. Acute cellular rejection (ACR) is difficult to distinguish from HCV recurrence, based on analysis of patient liver biopsies, as a result of common histological features. Previous studies comparing HCV

patients with and without ACR demonstrate that many of the Bortezomib repressed genes are significantly up-regulated during ACR in HCV patients.3, 14 Additionally, repression of innate and inflammatory genes was characteristic of HCV recurrence, rather than ACR, in HCV transplant patients.15 This indicates that though short-term clinical factors, such as ACR, may confound long-term efforts to develop molecular signatures of liver disease pathogenesis, repression

of these innate immune genes is more widespread and of greater magnitude. Immune repression early in infection PI3K inhibitor may contribute to increased hepatocyte infection during HCV recurrence and thus may create a more favorable environment for progression to severe disease. Although antigen presentation has been associated with HCV pathogenesis,16-18 these pathways are normally suppressed by allograft rejection drugs, causing impaired T-cell responses in HCV transplant patients. However, it is difficult to determine the effect of specific immunosuppressive regimens, because patients are routinely treated with different drugs and dosing regimens. Generally, the immunosuppressive regimens used are less likely to repress innate immune responses that could attenuate the severity of HCV recurrence. Innate immune

antagonism by HCV infection may result in the virus eliciting a transcriptional program that eventually results in fibrosis and disease progression, which is partially reflected by the increase in inflammatory genes over time caused by infiltrating leukocytes. HCV facilitates its replication by antagonizing the induction of antiviral interferons, ISGs, and antiviral cytokines through the action of the viral nonstructural protein (NS)3/4 protease and NS5A.19-22 Clinicians have not routinely treated HCV patients with post-OLT ribavirin and pegylated interferon, primarily because the high expense and harsh side effects of this treatment regimen do not justify its use in patients recovering from organ transplantation. However, Meloxicam a recent study demonstrated that post-OLT treatment resulted in stable or improved fibrosis scores, even in some patients who did not demonstrate sustained virologic response.23 Our data indicating that repressed antiviral gene expression early in infection determines transition to severe disease suggests that patients may benefit from early therapeutic intervention during HCV recurrence to boost innate immune genes not effected by immunosuppressant drugs during the first 3 months post-OLT. Early repression of cell-division mediators in patients who progress also indicates that these transcriptional profiles are altered.

This distinguishes this signature with regard to long-term outcome, compared to the clinical situation early post-OLT. Acute cellular rejection (ACR) is difficult to distinguish from HCV recurrence, based on analysis of patient liver biopsies, as a result of common histological features. Previous studies comparing HCV

patients with and without ACR demonstrate that many of the Midostaurin datasheet repressed genes are significantly up-regulated during ACR in HCV patients.3, 14 Additionally, repression of innate and inflammatory genes was characteristic of HCV recurrence, rather than ACR, in HCV transplant patients.15 This indicates that though short-term clinical factors, such as ACR, may confound long-term efforts to develop molecular signatures of liver disease pathogenesis, repression

of these innate immune genes is more widespread and of greater magnitude. Immune repression early in infection MS-275 chemical structure may contribute to increased hepatocyte infection during HCV recurrence and thus may create a more favorable environment for progression to severe disease. Although antigen presentation has been associated with HCV pathogenesis,16-18 these pathways are normally suppressed by allograft rejection drugs, causing impaired T-cell responses in HCV transplant patients. However, it is difficult to determine the effect of specific immunosuppressive regimens, because patients are routinely treated with different drugs and dosing regimens. Generally, the immunosuppressive regimens used are less likely to repress innate immune responses that could attenuate the severity of HCV recurrence. Innate immune

antagonism by HCV infection may result in the virus eliciting a transcriptional program that eventually results in fibrosis and disease progression, which is partially reflected by the increase in inflammatory genes over time caused by infiltrating leukocytes. HCV facilitates its replication by antagonizing the induction of antiviral interferons, ISGs, and antiviral cytokines through the action of the viral nonstructural protein (NS)3/4 protease and NS5A.19-22 Clinicians have not routinely treated HCV patients with post-OLT ribavirin and pegylated interferon, primarily because the high expense and harsh side effects of this treatment regimen do not justify its use in patients recovering from organ transplantation. However, Phosphatidylinositol diacylglycerol-lyase a recent study demonstrated that post-OLT treatment resulted in stable or improved fibrosis scores, even in some patients who did not demonstrate sustained virologic response.23 Our data indicating that repressed antiviral gene expression early in infection determines transition to severe disease suggests that patients may benefit from early therapeutic intervention during HCV recurrence to boost innate immune genes not effected by immunosuppressant drugs during the first 3 months post-OLT. Early repression of cell-division mediators in patients who progress also indicates that these transcriptional profiles are altered.