Although the study was open-label, the sponsor was blinded to tre

Although the study was open-label, the sponsor was blinded to treatment allocation and viral load results until treatment week 12. Patients were enrolled at 51 centers in the United States. Patients were stratified by serum HCV RNA titers (≤780,000 IU/mL or >780,000 IU/mL) and baseline weight (≤75 or >75 kg). An interactive voice response system was used to randomize patients in a 1:1:1:1 ratio to receive weight-based TBV 20 mg/kg/day, 25 mg/kg/day, or 30 mg/kg/day (Valeant Pharmaceuticals North America, Aliso Viejo, CA) or weight-based RBV at 800, 1000, 1200, or 1400 mg/day (Copegus; Selleckchem Alectinib Hoffmann-La

Roche, Nutley, NJ) in combination with peg-IFN alfa 2b (PegIntron; Schering Corp., Kenilworth, NJ). All patients received doses twice

daily with their morning and evening meals. Patients were treated for 48 weeks, but treatment was discontinued for evidence of nonresponse defined as <2-log decline at week 12 or a positive viral load at week 24. Study treatment was initiated on day 1 and clinic visits occurred at treatment weeks (TWs) 1, 2, 3, 4, 8, 12, 18, 24, 30, 36, and 48, as well as posttreatment follow-up weeks (FWs) 4, 12, 20, and 24. All patients who completed treatment with study drug or discontinued treatment prematurely (except nonresponders) immediately entered a 24-week follow-up period. The study protocol was approved by the institutional review boards of participating institutions and was conducted in accordance with the Declaration of Helsinki and provisions of Good Clinical Practices. All patients provided written Rapamycin chemical structure informed consent. The objective of this study was to select an optimal dose of TBV by comparing the efficacy and safety of three TBV dose levels MCE versus RBV based on body weight, both administered

with peg-IFN alfa-2b to therapy-naive compensated patients with genotype 1 chronic hepatitis C. The primary efficacy endpoint was early virologic response (EVR) defined as the proportion of patients with at least a 2-log decrease from baseline in serum HCV RNA levels at TW12. Additional efficacy endpoints assessed in the trial included SVR; undetectable HCV RNA at TW4, TW24, and TW48; and viral relapse for those who were responders at the end of treatment. Subgroup analyses were carried out to determine the impact of various baseline demographic factors such as sex, age, race, weight, baseline HCV RNA, and fibrosis score on response. Lack of efficacy was defined as less than a 2-log decrease of HCV RNA (IU/mL) at TW12 or detectable HCV RNA at TW24. Relapse rates were calculated by measuring the proportion of responding patients whose plasma HCV levels changed from undetectable at end of treatment to detectable at FW24. The primary safety endpoint was the proportion of patients with Hb < 10 g/dL at any time during the treatment period.

Although the study was open-label, the sponsor was blinded to tre

Although the study was open-label, the sponsor was blinded to treatment allocation and viral load results until treatment week 12. Patients were enrolled at 51 centers in the United States. Patients were stratified by serum HCV RNA titers (≤780,000 IU/mL or >780,000 IU/mL) and baseline weight (≤75 or >75 kg). An interactive voice response system was used to randomize patients in a 1:1:1:1 ratio to receive weight-based TBV 20 mg/kg/day, 25 mg/kg/day, or 30 mg/kg/day (Valeant Pharmaceuticals North America, Aliso Viejo, CA) or weight-based RBV at 800, 1000, 1200, or 1400 mg/day (Copegus; Lorlatinib Hoffmann-La

Roche, Nutley, NJ) in combination with peg-IFN alfa 2b (PegIntron; Schering Corp., Kenilworth, NJ). All patients received doses twice

daily with their morning and evening meals. Patients were treated for 48 weeks, but treatment was discontinued for evidence of nonresponse defined as <2-log decline at week 12 or a positive viral load at week 24. Study treatment was initiated on day 1 and clinic visits occurred at treatment weeks (TWs) 1, 2, 3, 4, 8, 12, 18, 24, 30, 36, and 48, as well as posttreatment follow-up weeks (FWs) 4, 12, 20, and 24. All patients who completed treatment with study drug or discontinued treatment prematurely (except nonresponders) immediately entered a 24-week follow-up period. The study protocol was approved by the institutional review boards of participating institutions and was conducted in accordance with the Declaration of Helsinki and provisions of Good Clinical Practices. All patients provided written LY2606368 purchase informed consent. The objective of this study was to select an optimal dose of TBV by comparing the efficacy and safety of three TBV dose levels MCE公司 versus RBV based on body weight, both administered

with peg-IFN alfa-2b to therapy-naive compensated patients with genotype 1 chronic hepatitis C. The primary efficacy endpoint was early virologic response (EVR) defined as the proportion of patients with at least a 2-log decrease from baseline in serum HCV RNA levels at TW12. Additional efficacy endpoints assessed in the trial included SVR; undetectable HCV RNA at TW4, TW24, and TW48; and viral relapse for those who were responders at the end of treatment. Subgroup analyses were carried out to determine the impact of various baseline demographic factors such as sex, age, race, weight, baseline HCV RNA, and fibrosis score on response. Lack of efficacy was defined as less than a 2-log decrease of HCV RNA (IU/mL) at TW12 or detectable HCV RNA at TW24. Relapse rates were calculated by measuring the proportion of responding patients whose plasma HCV levels changed from undetectable at end of treatment to detectable at FW24. The primary safety endpoint was the proportion of patients with Hb < 10 g/dL at any time during the treatment period.

[19] Notwithstanding the effectiveness of GON blockades

f

[19] Notwithstanding the effectiveness of GON blockades

for migrainuers,20-22 the mechanism(s) for the successful outcome remain uncertain.[23] It has been postulated that GON blockade influences central pain processing mechanisms by modulating responses to convergent synaptic input from cervical and trigeminal nociceptive afferents.[23] In our clinical experience, patients often report lessening of their referred, usual pain as the examination of the cervicospinal segment is sustained. The pain usually lessens (to a variable degree, but often with complete resolution) within 90 seconds. Moreover, sustaining the examination repeatedly results not only in decreasing intensity of head Selumetinib in vivo pain referral but also in more expeditious resolution. Furthermore, patients presenting with allodynia frequently report that after lessening of their referred pain, the allodynia has decreased

or resolved,24-26 perhaps indicating that a pre-existing central sensitization state had diminished. The purpose of the present study was to investigate cervical, interictal referral of usual head pain and its effect on the nBR in migraineurs. In particular, effects of PAIVMs of the AO and C2-3 spinal segments on referred head pain and trigeminal nociceptive activity were examined interictally. It was hypothesized that as referred check details head pain decreased, there would be a corresponding increase in latency and decrease in the AUC of R2, reflecting a decrease in excitability of the TCN. Fifteen volunteers participated

in the study (14 females, 1 male; age 24-44 years, mean age 33.3 years). All participants met the International Headache Society’s diagnostic classification criteria for migraine with or without aura, experiencing 2-8 attacks of migraine within the previous 3 months.[2] Each participant had been free from migraine for at least 24 hours. Informed consent was obtained from all participants, and the study was approved by the Ethics Committee of Murdoch University. The PAIVM examination was performed by a single clinician (D.H.W. – Musculoskeletal Physiotherapist) with 22 years of experience, whose medchemexpress practice is limited to examination and treatment of the upper cervical spine in primary headache conditions. Intra-examiner reliability was analyzed using Cohen’s Kappa in a previous study[27] that demonstrated perfect agreement in 17 of 22 PAIVM techniques. Of the 5 remaining tests, the lowest Kappa score was k = 0.667, P = .01, which indicated good agreement. Critical to our study was that usual head pain could be reproduced during the cervical examination. Therefore, to exclude participants who did not develop head pain during this procedure, an “inclusion/exclusion” examination was performed prior to commencing the study.

We have therefore assessed whether there is a significant associa

We have therefore assessed whether there is a significant association between liver histology and smoking patterns among patients with biopsy-proven NAFLD. A total of 90 consecutive outpatients with NAFLD (43 males and 47 females, mean age, 47 ± 8 years) were recruited from our clinics. All patients had chronically elevated liver enzymes and hepatic steatosis detected by ultrasonography. The NAFLD diagnosis was based on liver biopsy and exclusion of other known MAPK Inhibitor high throughput screening etiologic factors of chronic liver disease (alcohol abuse or intake ≥20 g/day, viral hepatitis, autoimmune

hepatitis, and use of hepatotoxic drugs). An experienced pathologist blinded to clinical data scored the liver biopsies according to the National Institute of Diabetes and Digestive and Kidney Diseases NASH Clinical Research Network scoring system.3 Pack-years of smoking were calculated as the product of the duration of smoking (in RO4929097 years) and the average number of cigarettes smoked per day. The protocol was approved by the local ethics committee, and all participants gave written informed consent. In multivariable-adjusted linear logistic regression models, each histological feature of NAFLD (i.e., steatosis grade, necroinflammatory grade, or fibrosis stage analyzed separately)

was considered as the dependent variable. Sex, age, body mass index, smoking, low-density lipoprotein cholesterol, homeostasis model assessment of insulin resistance (HOMA-IR) score, and metabolic syndrome (considered as a single clinical entity) were included as covariates. A total of 30 patients had ever smoked, 26 were past

smokers, whereas 34 were current smokers. The distribution of nonsmokers, past smokers, and current smokers was not different in NAFLD patients classified according to liver histopathology (steatosis alone, borderline steatohepatitis, definite steatohepatitis). Notably, pack-years of smoking were not associated with degree of MCE公司 hepatic steatosis (P = 0.67), necroinflammation (P = 0.34), and fibrosis among patients with NAFLD (P = 0.41). These results suggest that the severity of liver histopathology among patients with NAFLD is not associated with smoking patterns, after allowance for classical risk factors, insulin resistance, and the presence of the metabolic syndrome. This study has shown for the first time that the histological severity of NAFLD is not independently predicted by smoking patterns after adjustment for a broad spectrum of potential confounders, including the metabolic syndrome, a condition that is strongly correlated with NAFLD. Cigarette smoking is one of the major environmental factors suggested to play a crucial role in the development of several diseases.4 Disorders such as atherosclerosis, lung cancer, or cardiovascular diseases are highly associated with tobacco consumption.

We have therefore assessed whether there is a significant associa

We have therefore assessed whether there is a significant association between liver histology and smoking patterns among patients with biopsy-proven NAFLD. A total of 90 consecutive outpatients with NAFLD (43 males and 47 females, mean age, 47 ± 8 years) were recruited from our clinics. All patients had chronically elevated liver enzymes and hepatic steatosis detected by ultrasonography. The NAFLD diagnosis was based on liver biopsy and exclusion of other known http://www.selleckchem.com/products/mi-503.html etiologic factors of chronic liver disease (alcohol abuse or intake ≥20 g/day, viral hepatitis, autoimmune

hepatitis, and use of hepatotoxic drugs). An experienced pathologist blinded to clinical data scored the liver biopsies according to the National Institute of Diabetes and Digestive and Kidney Diseases NASH Clinical Research Network scoring system.3 Pack-years of smoking were calculated as the product of the duration of smoking (in Dabrafenib purchase years) and the average number of cigarettes smoked per day. The protocol was approved by the local ethics committee, and all participants gave written informed consent. In multivariable-adjusted linear logistic regression models, each histological feature of NAFLD (i.e., steatosis grade, necroinflammatory grade, or fibrosis stage analyzed separately)

was considered as the dependent variable. Sex, age, body mass index, smoking, low-density lipoprotein cholesterol, homeostasis model assessment of insulin resistance (HOMA-IR) score, and metabolic syndrome (considered as a single clinical entity) were included as covariates. A total of 30 patients had ever smoked, 26 were past

smokers, whereas 34 were current smokers. The distribution of nonsmokers, past smokers, and current smokers was not different in NAFLD patients classified according to liver histopathology (steatosis alone, borderline steatohepatitis, definite steatohepatitis). Notably, pack-years of smoking were not associated with degree of 上海皓元医药股份有限公司 hepatic steatosis (P = 0.67), necroinflammation (P = 0.34), and fibrosis among patients with NAFLD (P = 0.41). These results suggest that the severity of liver histopathology among patients with NAFLD is not associated with smoking patterns, after allowance for classical risk factors, insulin resistance, and the presence of the metabolic syndrome. This study has shown for the first time that the histological severity of NAFLD is not independently predicted by smoking patterns after adjustment for a broad spectrum of potential confounders, including the metabolic syndrome, a condition that is strongly correlated with NAFLD. Cigarette smoking is one of the major environmental factors suggested to play a crucial role in the development of several diseases.4 Disorders such as atherosclerosis, lung cancer, or cardiovascular diseases are highly associated with tobacco consumption.

We have therefore assessed whether there is a significant associa

We have therefore assessed whether there is a significant association between liver histology and smoking patterns among patients with biopsy-proven NAFLD. A total of 90 consecutive outpatients with NAFLD (43 males and 47 females, mean age, 47 ± 8 years) were recruited from our clinics. All patients had chronically elevated liver enzymes and hepatic steatosis detected by ultrasonography. The NAFLD diagnosis was based on liver biopsy and exclusion of other known http://www.selleckchem.com/products/smoothened-agonist-sag-hcl.html etiologic factors of chronic liver disease (alcohol abuse or intake ≥20 g/day, viral hepatitis, autoimmune

hepatitis, and use of hepatotoxic drugs). An experienced pathologist blinded to clinical data scored the liver biopsies according to the National Institute of Diabetes and Digestive and Kidney Diseases NASH Clinical Research Network scoring system.3 Pack-years of smoking were calculated as the product of the duration of smoking (in Lapatinib chemical structure years) and the average number of cigarettes smoked per day. The protocol was approved by the local ethics committee, and all participants gave written informed consent. In multivariable-adjusted linear logistic regression models, each histological feature of NAFLD (i.e., steatosis grade, necroinflammatory grade, or fibrosis stage analyzed separately)

was considered as the dependent variable. Sex, age, body mass index, smoking, low-density lipoprotein cholesterol, homeostasis model assessment of insulin resistance (HOMA-IR) score, and metabolic syndrome (considered as a single clinical entity) were included as covariates. A total of 30 patients had ever smoked, 26 were past

smokers, whereas 34 were current smokers. The distribution of nonsmokers, past smokers, and current smokers was not different in NAFLD patients classified according to liver histopathology (steatosis alone, borderline steatohepatitis, definite steatohepatitis). Notably, pack-years of smoking were not associated with degree of 上海皓元 hepatic steatosis (P = 0.67), necroinflammation (P = 0.34), and fibrosis among patients with NAFLD (P = 0.41). These results suggest that the severity of liver histopathology among patients with NAFLD is not associated with smoking patterns, after allowance for classical risk factors, insulin resistance, and the presence of the metabolic syndrome. This study has shown for the first time that the histological severity of NAFLD is not independently predicted by smoking patterns after adjustment for a broad spectrum of potential confounders, including the metabolic syndrome, a condition that is strongly correlated with NAFLD. Cigarette smoking is one of the major environmental factors suggested to play a crucial role in the development of several diseases.4 Disorders such as atherosclerosis, lung cancer, or cardiovascular diseases are highly associated with tobacco consumption.

TNF-α induced a relocalization of tight junction protein occludin

TNF-α induced a relocalization of tight junction protein occludin and increased

the lateral diffusion speed of HCV receptor tetraspanin CD81 in polarized HepG2 cells, providing a mechanism for their increased permissivity to support HCV entry. High concentrations of HCV particles could stimulate macrophages to express TNF-α, providing a direct mechanism for the virus to promote infection. Conclusion: This study shows a new role for TNF-α to increase virus entry and highlights the potential for HCV to exploit existing innate immune responses in the liver to promote de novo infection events. (Hepatology 2014;59:1320-1330) “
“Background and Aim:  The widely accepted range of upper limits of normal (ULN) alanine aminotransferase (ALT) levels (ULN < 40 U/L) was recently challenged by several reports. Both ALT and aspartate aminotransferase Sotrastaurin cost (AST) are commonly used as surrogate markers of liver disease, but almost all studies of aminotransferase activity were conducted on ALT. We investigated not only ULN of ALT but Dasatinib manufacturer also AST activity and to identify factors modulating them in healthy Korean. Methods:  A cross-sectional study of 411 240 registered blood donors in all nationwide blood banks belonging to the Korean Red Cross were conducted. ULN of ALT and AST was evaluated adjusting their age according to the national population census database.

“Decision tree model” was used to identify the affecting factors of ALT and AST and optimal cut-off points of affecting factors. Results:  “ULN of ALT” was 34 U/L in men and 24 U/L in women and “ULN of AST” was 32 U/L in men and 26 U/L in women in the blood donor database. Decision tree analysis showed that ALT levels

were mostly influenced by body mass index level and its critical two cut-off points were 23.5 kg/m2 and 25.8 kg/m2, respectively. The most affecting factor of AST was gender. Conclusion:  Upper limits of normal of ALT and AST in Koreans were lower than conventional accepted values (< 40 U/L) but higher than recently suggested values (male < 30 U/L and female < 19 U/L). Body mass index was the most determining factor for ALT and gender was the most influencing factor for AST activity. "
“Nonsteroidal anti-inflammatory drugs (NSAIDs), including low-dose aspirin, medchemexpress are very frequently prescribed in older patients in order to palliate or prevent age-related degenerative joint diseases or cardiovascular events. From the perspective of the gastrointestinal system, their most frequent serious adverse effect is hemorrhage from gastric or duodenal ulcers, occurring overall in about 0.5–2.0% per patient year of continuous use. Much more common are gastric erosions – at least a few will be found in most patients if an endoscopy is performed – but these usually heal uneventfully and are normally asymptomatic. Dyspepsia is a common side-effect but there is little correlation with the macroscopic injury and the pathogenetic mechanisms are less well understood.

TNF-α induced a relocalization of tight junction protein occludin

TNF-α induced a relocalization of tight junction protein occludin and increased

the lateral diffusion speed of HCV receptor tetraspanin CD81 in polarized HepG2 cells, providing a mechanism for their increased permissivity to support HCV entry. High concentrations of HCV particles could stimulate macrophages to express TNF-α, providing a direct mechanism for the virus to promote infection. Conclusion: This study shows a new role for TNF-α to increase virus entry and highlights the potential for HCV to exploit existing innate immune responses in the liver to promote de novo infection events. (Hepatology 2014;59:1320-1330) “
“Background and Aim:  The widely accepted range of upper limits of normal (ULN) alanine aminotransferase (ALT) levels (ULN < 40 U/L) was recently challenged by several reports. Both ALT and aspartate aminotransferase selleck chemicals (AST) are commonly used as surrogate markers of liver disease, but almost all studies of aminotransferase activity were conducted on ALT. We investigated not only ULN of ALT but MAPK Inhibitor Library chemical structure also AST activity and to identify factors modulating them in healthy Korean. Methods:  A cross-sectional study of 411 240 registered blood donors in all nationwide blood banks belonging to the Korean Red Cross were conducted. ULN of ALT and AST was evaluated adjusting their age according to the national population census database.

“Decision tree model” was used to identify the affecting factors of ALT and AST and optimal cut-off points of affecting factors. Results:  “ULN of ALT” was 34 U/L in men and 24 U/L in women and “ULN of AST” was 32 U/L in men and 26 U/L in women in the blood donor database. Decision tree analysis showed that ALT levels

were mostly influenced by body mass index level and its critical two cut-off points were 23.5 kg/m2 and 25.8 kg/m2, respectively. The most affecting factor of AST was gender. Conclusion:  Upper limits of normal of ALT and AST in Koreans were lower than conventional accepted values (< 40 U/L) but higher than recently suggested values (male < 30 U/L and female < 19 U/L). Body mass index was the most determining factor for ALT and gender was the most influencing factor for AST activity. "
“Nonsteroidal anti-inflammatory drugs (NSAIDs), including low-dose aspirin, medchemexpress are very frequently prescribed in older patients in order to palliate or prevent age-related degenerative joint diseases or cardiovascular events. From the perspective of the gastrointestinal system, their most frequent serious adverse effect is hemorrhage from gastric or duodenal ulcers, occurring overall in about 0.5–2.0% per patient year of continuous use. Much more common are gastric erosions – at least a few will be found in most patients if an endoscopy is performed – but these usually heal uneventfully and are normally asymptomatic. Dyspepsia is a common side-effect but there is little correlation with the macroscopic injury and the pathogenetic mechanisms are less well understood.

These results were associated with increased expression of endoth

These results were associated with increased expression of endothelin-1 and its receptor, together with e-NOS up-regulation as potential mechanisms of protection. Taking into account these experiments, it is plausible

that CIH effects on vascular reactivity could be attenuated in the CBDL model, such as in sustained chronic hypoxia. On the other hand, further vasoconstriction to Mtx was observed in both models of cirrhosis after CIH. Our results suggest that additional factors CH5424802 datasheet may play a role in this response. Particularly, increased production of endothelin-1 has been found to occur during CIH.34 To our knowledge, this is the first experimental study investigating the hepatic hemodynamic effects of CIH in the setting of cirrhosis. Our novel findings are clinically relevant, because CIH and OSAS have been described in patients with cirrhosis and portal hypertension. A pilot study showed a previously undescribed high prevalence of OSAS and nocturnal oxygen desaturations among patients who have cirrhosis with ascites that improved after paracenthesis.10 This observation has been

confirmed by other groups more recently.11, 13 The results of these studies showed that OSAS can be present in cirrhotic patients and particularly in those with severe liver disease, which could exacerbate impairment of liver function. In fact, OSAS has been associated with elevated alanine aminotransferase levels in patients12 and animals exposed to CIH.35 Furthermore, even severe histology changes (inflammation and fibrosis) have been shown to appear after long exposure to selleck kinase inhibitor CIH.35 In our short-term experimental conditions, medchemexpress the

absence of change in baseline portal perfusion pressure makes a change in intrahepatic mechanical vascular resistance unlikely due to increased fibrosis. In vivo baseline hemodynamic parameters were not significantly different between CIH and HC rats. However, after volume expansion was performed in cirrhotic rats, analysis of hemodynamics yielded interesting results. As shown by other investigators,16, 36 after volume expansion in cirrhotic rats, PP increases as MAP and portal blood flow augments, due to the inability of the liver circulation to appropriately dilate in response to flow. In fact, this further increase in PP can be prevented with NO donors16, 36 without modifying MAP or portal blood flow. In our study, PP increase was similar in CIH and HC rats. However, MAP and probably PBF increase were lower in CIH rats. Indeed, vascular hyporeactivity due to autonomic impairment has been described recently after exposure to CIH.37 These observations suggest that CIH may also provoke additional deleterious systemic effects in cirrhotic rats, yet to be studied. Overall, these data suggest that CIH could be a relevant underestimated factor to take into account when assessing cirrhotic patients with portal hypertension.

These results were associated with increased expression of endoth

These results were associated with increased expression of endothelin-1 and its receptor, together with e-NOS up-regulation as potential mechanisms of protection. Taking into account these experiments, it is plausible

that CIH effects on vascular reactivity could be attenuated in the CBDL model, such as in sustained chronic hypoxia. On the other hand, further vasoconstriction to Mtx was observed in both models of cirrhosis after CIH. Our results suggest that additional factors X-396 manufacturer may play a role in this response. Particularly, increased production of endothelin-1 has been found to occur during CIH.34 To our knowledge, this is the first experimental study investigating the hepatic hemodynamic effects of CIH in the setting of cirrhosis. Our novel findings are clinically relevant, because CIH and OSAS have been described in patients with cirrhosis and portal hypertension. A pilot study showed a previously undescribed high prevalence of OSAS and nocturnal oxygen desaturations among patients who have cirrhosis with ascites that improved after paracenthesis.10 This observation has been

confirmed by other groups more recently.11, 13 The results of these studies showed that OSAS can be present in cirrhotic patients and particularly in those with severe liver disease, which could exacerbate impairment of liver function. In fact, OSAS has been associated with elevated alanine aminotransferase levels in patients12 and animals exposed to CIH.35 Furthermore, even severe histology changes (inflammation and fibrosis) have been shown to appear after long exposure to LY2606368 price CIH.35 In our short-term experimental conditions, 上海皓元医药股份有限公司 the

absence of change in baseline portal perfusion pressure makes a change in intrahepatic mechanical vascular resistance unlikely due to increased fibrosis. In vivo baseline hemodynamic parameters were not significantly different between CIH and HC rats. However, after volume expansion was performed in cirrhotic rats, analysis of hemodynamics yielded interesting results. As shown by other investigators,16, 36 after volume expansion in cirrhotic rats, PP increases as MAP and portal blood flow augments, due to the inability of the liver circulation to appropriately dilate in response to flow. In fact, this further increase in PP can be prevented with NO donors16, 36 without modifying MAP or portal blood flow. In our study, PP increase was similar in CIH and HC rats. However, MAP and probably PBF increase were lower in CIH rats. Indeed, vascular hyporeactivity due to autonomic impairment has been described recently after exposure to CIH.37 These observations suggest that CIH may also provoke additional deleterious systemic effects in cirrhotic rats, yet to be studied. Overall, these data suggest that CIH could be a relevant underestimated factor to take into account when assessing cirrhotic patients with portal hypertension.