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1.

Background

Nonalcoholic fatty liver disease (NAFLD) is one of the most common reasons of enzyme increase in liver. In About 10 percent of patients with NAFLD, the disease progresses toward Non Alcoholic Steatohepatitis (NASH) and about one third of them may progress toward cirrhosis, liver dysfunction, and even hepatocellular carcinoma.

Objectives

According to high prevalence of NAFLD and the fact that there is no consensus on treatment of this disease, the aim of this study was to assess the effects of metformin, pioglitazone, and silymarin on treatment of NAFLD.

Patients and Methods

Sixty six patients with NAFLD who were presented in the Endocrinology and Metabolism clinic of Boo’ali Hospital, Qazvin, Iran, were assigned randomly into three groups (n = 22). First group was treated by pioglitazone 15 mg/d, second group by metformin 500 mg/d, and third group by silymarin 140 mg/d. All patients underwent clinical and biochemical evaluations including weight, fasting blood sugar (FBS), lipid profiles, body mass index (BMI), aspartate aminotransferase (AST ), alanine aminotransferase (ALT), and serum insulin levels in pre- and post-intervention after eight-week follow up.

Results

Before the treatment there was no significant difference between three groups with respect to average age, BMI and gender, FBS, lipid profile, AST, ALT, serum insulin level, and Homeostasis Model Assessment (HOMA) index for insulin resistance. After the intervention, a significant reduction was observed in average amount of FBS, lipid profile, ALT, AST, serum insulin level and HOMA index in three groups (P < 0.01). The most reduction in average FBS, TG, serum insulin level, and HOMA index was observed in pioglitazone group, the most reduction in average amount of cholesterol was seen in metformin group, and the most decrease in average amount of AST and ALT occurred in silymarin group.

Conclusions

These results suggest that all drugs are beneficial in improving biochemical indices in patients with NAFLD. Changes in AST and ALT in silymarin group were demonstrated more than that in other groups and the average difference between changes was significant between silymarin and metformin groups.  相似文献   

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Context

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, with 5-10% of liver having extra fat. Increase in its prevalence in all age groups is linked with obesity and Type II diabetes. The treatment of NAFLD remains controversial. A growing body of evidence suggests a relation between overgrowth of gut microbiota with NAFLD and non-alcoholic steatohepatitis (NASH). The objective of this review is to provide an overview on experimental and clinical studies assessing all positive and negative effects of probiotics.

Evidence Acquisition

We made a critical appraisal on various types of documents published from 1999 to March 2012 in journals, electronic books, seminars, and symposium contexts including Medline, PubMed, and Cochrane Central Register of Controlled Trials databases. We used the key words: “non-alcoholic fatty liver disease, probiotics, non-alcoholic steatohepatitis, liver disease, and fatty liver”.

Results

Probiotics, as biological factors, control the gut microbiota and result in its progression. It is in this sense that they are suggestive of a new and a natural way of promoting liver function. Correspondingly, limited evidence suggests that probiotics could be considered as a new way of treatment for NAFLD.

Conclusions

Various experimental studies and clinical trials revealed promising effects of probiotics in improving NAFLD; however given the limited experience in this field, generalization of probiotics as treatment of NAFLD needs substantiation through more trials with a larger sample sizes and with longer-term follow up.  相似文献   

4.
Background: Pro-inflammatory cytokines are associated with systemic inflammatory responses. Objective: To investigate the levels of pro-inflammatory cytokines (IL-1b, IL-6, and TNF-a) in patients with non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) compared to healthy individuals. Methods: This case-control study was conducted on 30 patients with NAFL, 30 patients with NASH, and 30 healthy volunteers. The plasma level of IL-1b, IL-6, and TNF-a were determined by ELISA, and biochemical parameters were measured using colorimetric methods. Results: IL-1b and IL-6 levels were significantly higher in patients with NASH compared with NAFL and control group. However, TNF-a levels had no significant variations in NAFL and NASH patients compared to the control group (p=0.903 and p=0.960, respectively). Conclusion: Results showed that the levels of ALT activity and pro-inflammatory cytokines were higher in patients with NASH compared to control and NAFL subjects; Therefore, steatosis and inflammation develop as a result of excessive pro-inflammatory factors in NASH.  相似文献   

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Background: Functional dyspepsia (FD) is defined as persistent or recurrent pain/discomfort centred in the upper abdomen, where no structural explanation for the symptoms is found. The role of drug treatment remains controversial. The aim in this study was to evaluate the effect of omeprazole 20 mg twice daily (b.i.d) and to test methods for symptom assessment. Methods: 197 patients fulfilling the criteria for FD were randomly allocated to double-blind treatment with omeprazole 20 mg b.i.d ( n = 100) or placebo ( n = 97) for 14 days. Patients with a known gastrointestinal disorder or with main symptoms indicating gastro-oesophageal reflux disease or irritable bowel syndrome were excluded. Helicobacter pylori testing and 24-h intra-oesophageal 24-h pH-metry were performed before randomization. The patients recorded dyspeptic symptoms on diary cards. Results: A stringent endpoint, 'complete symptom relief on the last day of treatment', was the primary efficacy variable. For the APT cohort, this was achieved in 29.0% and 17.7% on omeprazole and placebo, respectively (95% CI of difference (11.3%): -0.4%-23.0%, P = 0.057). Similar figures in the PP cohort were 31.0% and 15.5%, respectively (95% CI of difference (15.5%): 3.2%-27.7%, P = 0.018). The benefit of omeprazole in the PP cohort was confirmed by secondary endpoints such as, no dyspeptic symptoms on the last 2 days of treatment and overall treatment response. H. pylori status and the level of oesophageal acid exposure did not significantly influence the response to therapy. Conclusion: A subset of patients with FD will respond to therapy with omeprazole.  相似文献   

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脂肪性肝病:愈来愈严重的全球性公共卫生问题   总被引:2,自引:0,他引:2  
曹海霞  范建高 《胃肠病学》2011,16(3):129-130
脂肪性肝病分为酒精性肝病和非酒精性脂肪性肝病,其发病率呈逐年上升趋势,目前认为是终末期肝病的主要病因之一,正成为世界范围内威胁人类健康的重大问题。深入探讨其发病机制,揭示疾病特点,将有助于提高脂肪性肝病的诊治水平,从而改善人类健康、减少社会经济负担。  相似文献   

8.

Background:

Obstructive sleep apnea (OSA) is a major disease that can cause significant mortality and morbidity. Chronic intermittent hypoxia is a potential causal factor in the progression from fatty liver to nonalcoholic steatohepatitis.

Objectives:

This study evaluated the association between the degree of liver steatosis and severity of nocturnal hypoxia.

Patients and Methods:

In this study, between December 2011 and December 2013, patients with ultrasound-diagnosed NAFLD evaluated by standart polysomnography were subsequentally recorded. Patients with alcohol use, viral hepatitis and other chronic liver diseases were excluded. We analyzed polysomnographic parameters, steatosis level and severity of obstructive sleep apnea (OSA) in consideration of body mass index (BMI), biochemical tests and ultrasonographic liver data of 137 subjects. Patients with sleep apnea and AHI scores of < 5, 5 - 14, 15 - 29 and ≥30 are categorized as control, mild, moderate and severe, respectively.

Results:

One hundred and thirty-seven patients (76 women, 61 men) with a mean age of 55.75 ± 10.13 years who underwent polysomnography were included in the study. Of 118 patients diagnosed with OSA, 19 (16.1%) had mild OSA, 39 (33.1%) moderate OSA and 60 (50.8%) severe OSA. Nineteen cases formed the control group. Apnea/hypopnea index and oxygen desaturation index (ODI) values were significantly higher in moderate and severe non-alcoholic fatty liver disease (NAFLD) compared to the non-NAFLD group. Mean nocturnal SpO2 values were significantly lower in mild NAFLD and severe NAFLD compared to the non-NAFLD group. Lowest O2 saturation (LaSO2) was found low in mild, moderate and severe NAFLD compared to the non-NAFLD group in a statistically significant manner.

Conclusions:

We assessed polysomnographic parameters of AHI, ODI, LaSO2 and mean nocturnal SpO2 levels, which are especially important in the association between NAFLD and OSAS. We think that it is necessary to be attentive regarding NAFLD development and progression in patients with OSA whose nocturnal hypoxia is severe.  相似文献   

9.

Background:

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disorder in western countries and an important cause of liver cirrhosis, as well as liver failure. Up to now, 20‒40% of the individuals suffer from this disorder and its prevalence is estimated around 5‒30% in Asia. The NAFLD is one of the most prevalent causes for increases in liver enzymes and has a close relationship with obesity, dyslipidemia, hypertension, and type II diabetes. However, no definite treatment has been identified for it yet.

Objectives:

The present study aimed to investigate the effect of berberis vulgaris extract in inducing changes in liver enzymes levels.

Patients and Methods:

The present clinical trial was conducted on 80 patients, including 32 males (40%) and 48 females (60%), who were randomly assigned into two groups of case and control. All the patients had ultrasound evidence of lipid accumulation in the liver and increases in liver enzymes. The case group received two capsules (750 mg) containing berberis vulgaris extract every day for 3 months, while the control group was treated with placebo. The weight, liver transaminases levels and lipid profiles of the two groups were assessed before, during, and after the study.

Results:

In the case group, the mean serum levels of alanine transaminase (ALT) and aspartate transaminase (AST) decreased from 49 to 27.48 and 48.22 to 29.8 u/L, respectively, which was statistically significant compared to the control group (P < 0.001, P < 0.001). In the control group, the mean of ALT and AST decreased from 50.4 to 46.8 and 45.7 to 44.9 u/L, respectively. The difference was not statistically significant. In addition, a significant decrease was observed in weight, triglycerides, and cholesterol, while no significant change was found in fasting blood sugar, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL).

Conclusions:

Considering the significant decrease in the liver enzymes, triglycerides and cholesterol after using berberis vulgaris extract, further studies with larger sample sizes will identify the accurate dose as well as duration of consumption for this extract, to recommend in the treatment of patients with NAFLD.  相似文献   

10.
The results of experimental and clinical studies support the hypothesis that gut-derived endotoxins might be of relevance for the development and course of alcoholic liver disease. The aim of this study was to test the effect of a nonabsorbable, broad-spectrum antibiotic on endotoxemia in patients with alcoholic liver disease. Fifty patients with alcoholic liver disease (27 with cirrhosis, 23 without cirrhosis) were randomly assigned to receive either paromomycin sulfate (3 × 1 g/day) or placebo in a double-blind fashion for at least 3 weeks, and if possible 4 weeks. Endotoxin concentration, liver function tests, and other laboratory parameters were determined in weekly intervals. Endotoxin concentration was also determined in 15 healthy controls. Groups receiving paromomycin or placebo were similar for clinical and biological items collected initially. Mean initial endotoxin concentrations were significantly elevated in both groups (mean ± SEM; paromomycin, 16.7 ± 5.3 pg/ml; placebo, 17.5 ± 6.9 pg/ml; healthy controls, 2.3 ± 0.4 pg/ml). Although the mean endotoxin concentration was lower in the verum group after 1 week (paromomycin, 8.0 ± 1.9 pg/ml; placebo, 14.6 ± 3.5 pg/ml; p > 0.05), paromomycin treatment had no significant effect on endotoxin concentration or liver function tests during the 4-week period. The beneficial effect of paromomycin treatment on endotoxemia in cirrhotics reported in earlier studies could not be reproduced under the conditions of this trial in patients with alcoholic liver disease.  相似文献   

11.

Background

The role of Helicobacter pylori (HP) in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) is unclear.

Objectives

The aim of this study was to evaluate the effect of HP eradication on liver fat content (LFC), liver function tests (LFT), lipid profile, and homeostasis model assessment-IR (HOMA-IR) index in NAFLD.

Patients and Methods

Dyspeptic patients with increased serum aminotransferase levels were enrolled in the study. The exclusion criteria were factors affecting serum aminotransferase or HP treatment strategy. Participants with persistent elevated serum aminotransferase level and ultrasound criteria for identification of fatty liver were presumed to have NAFLD. “NAFLD liver fat score” was used to classify NAFLD. Those with “NAFLD liver fat score” greater than -0.64 and positive results for urea breath test (UBT), were included. Lifestyle modification was provided to all participants. HP eradication was performed in intervention arm. LFC, fasting serum glucose (FSG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride (TG), cholesterol (CHOL), high and low-density lipoprotein (HDL, LDL), and HOMA-IR were checked at baseline and after that, at intervals of eight weeks and twenty four weeks.

Results

One hundred (49 males) patients with the mean age of 43.46 (± 11.52) were studied. Repeated measure ANOVA showed a significant reduction in LFC, anthropometric measurements, and laboratory parameters (except for HDL) in the both groups during the study; however, no significant difference was observed between the groups.

Conclusions

It seems that HP eradication per se might not affect LFC, LFT, lipid profile, and insulin resistance in dyspeptic NAFLD patients.  相似文献   

12.
Multiple therapeutic modalities have been used to treat hepatic encephalopathy. l-Acetylcarnitine (LAC) is a physiologically active substance that improves both the energetic and the neurotransmission profiles. LAC is able to cross the hematoencephalic barrier and reach the cerebral regions, where the acetylic group may be utilized. The aim of this work was to evaluate the efficacy of LAC in the treatment of hepatic coma in cirrhotic patients. Twenty-four suitably selected patients were enrolled in the study and, following randomization, received either LAC (n=13) or placebo (n=11). Statistically significant differences in neurological findings, as evaluated by the Glasgow Scale, as well as in ammonia serum levels and BUN were found following LAC treatment. In the placebo group we observed two cases of improved neurological findings as well as one case of improved EEG grading. In the other group we observed an improvement of neurological findings and of EEG grade in 10 and 8 subjects, respectively. Noteworthily, seven (54%) patients went from grade 4 down to grade 3, and one from grade 4 down to grade 1. The improvement in the neurological picture was evident at between 1 and 4 hr after the end of treatment, remaining until 24 hr after. No side effects were observed in our study series. Our study demonstrates that LAC administration improved neurological and biohumoral symptoms in selective cirrhotic patients with hepatic coma.  相似文献   

13.
目的系统评价儿童和青少年维生素D水平和非酒精性脂肪性肝病(NAFLD)的相关性。方法计算机检索PubMed、Cochrane Library、Embase数据库以及CNKI、中国生物医学文献数据库、万方和维普数据库,收集有关儿童及青少年维生素D水平与NAFLD之间关系的研究,检索时限从建库到2020年8月。按照纽卡斯尔-渥太华量表(NOS)进行文献质量评价,采用RevMan 5.3软件进行数据分析。结果Meta分析最终纳入10篇文献,NAFLD组共622例,健康对照组共1608例。10篇纳入研究的NOS评分均≥6分。10篇文献采用随机效应模型合并(I2=97%,P<0.05),NAFLD组血清25(OH)D水平显著低于对照组,差异有统计学意义(SMD=-1.40,95%CI:-2.07~-0.72)。结论儿童和青少年NAFLD患者血清中25(OH)D水平显著降低,其可能与NAFLD的进展和严重程度有关。  相似文献   

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Background and objectives: Increased plasma total homocysteine is a graded, independent risk factor for the development of atherosclerosis and thrombosis. More than 90% of patients with end-stage renal disease have hyperhomocysteinemia despite vitamin supplementation. It was shown in previous studies that a single intravenous dose of mesna 5 mg/kg caused a drop in plasma total homocysteine that was significantly lower than predialysis levels 2 d after dosing. It was hypothesized 5 mg/kg intravenous mesna administered thrice weekly, before dialysis, for 8 wk would cause a significant decrease in plasma total homocysteine compared with placebo.Design, setting, participants, & measurements: Patients with end-stage renal disease were randomly assigned to receive either intravenous mesna 5 mg/kg or placebo thrice weekly before dialysis. Predialysis plasma total homocysteine concentrations at weeks 4 and 8 were compared between groups by paired t test.Results: Mean total homocysteine at 8 wk in the placebo group was 24.9 μmol/L compared with 24.3 μmol/L in the mesna group (n = 22 [11 pairs]; mean difference 0.63). Interim analysis at 4 wk also showed no significant difference between mesna and placebo (n = 32 [16 pairs]; placebo 26.3 μmol/L, mesna 24.5 μmol/L; mean difference 1.88). Multivariable adjustments for baseline characteristics did not alter the analysis. Plasma mesna seemed to reach steady-state concentrations by 4 wk.Conclusions: It is concluded that 5 mg/kg mesna does not lower plasma total homocysteine in hemodialysis patients and that larger dosages may be required.Homocysteine (Hcy) is a non–protein-forming, thiol amino acid derived from dietary methionine after its ATP-dependent activation and subsequent transmethylation of biologically important molecules. Hcy is found in the plasma of all mammals, and the term “total homocysteine” (tHcy) is used to describe a composite of free (sulfhydryl), protein-disulfide bound, and homocysteine-cysteine and other mixed disulfide species (1).In the past two decades, retrospective and prospective studies have reported plasma tHcy as a graded, independent risk factor for cardiovascular and cerebrovascular disease (25). Meta-analysis of cohort studies suggested that a lowering of Hcy by 25% (approximately 3 μmol/L) may be associated with an 11% lower risk for coronary heart disease (odds ratio [OR] 0.89; 95% confidence interval [CI] 0.83 to 0.96) and a 19% lower risk for stroke (OR 0.81; 95% CI 0.69 to 0.95) (6), although this has yet to be corroborated in randomized, controlled trials. Elevated plasma tHcy (hyperhomocysteinemia) is almost universal among patients who have ESRD and require hemodialysis (712). Hyperhomocysteinemia has been linked with increased risk for both fatal and nonfatal cardiovascular events (3), as well as vascular access thrombosis (13,14), the most common cause for hospitalization of hemodialysis patients (15).Strategies for normalizing plasma tHcy concentration in ESRD have included increasing dialysis membrane pore size (10,16) and pharmacologic doses of water-soluble vitamins, including folic acid, vitamin B6, and vitamin B12 (17,18). Although vitamin therapy has been shown to lower plasma tHcy by 15 to 47% (1820), the majority of investigations failed to normalize plasma tHcy to levels observed in healthy control subjects with normal kidney function (9,17,18,2022). This was highlighted in the recently completed Homocysteinemia in Kidney and End Stage Renal Disease (HOST) trial by the inability of high-dosage folic acid and B vitamins to normalize plasma tHcy or affect cardiovascular outcomes (23). The results of the HOST trial along with other large randomized, controlled trials of patients with normal kidney function, including the Heart Outcomes Prevention Evaluation 2 (HOPE-2) trial (24), Norwegian Vitamin Trial (NORVIT) (25), and Vitamin Intervention for Stroke Prevention (VISP) trial (26), have led to the suggestion that investigation of nonvitamin therapies are needed to determine whether decreasing tHcy reduces the risk for atherosclerosis and thrombosis and their associated complications (27).Between 70 and 80% of plasma tHcy resides covalently bound via a disulfide bond to the single free cysteine residue on albumin (Cys34-albumin), limiting its availability for dialytic clearance (28,29). An emerging strategy to lower tHcy is to increase its free fraction within the blood, thereby improving its removal by dialysis. This can be achieved by the addition of a pharmaceutical agent that is capable of forming a sulfhydryl within the plasma and that will exchange with Cys34-albumin bound Hcy, allowing Hcy to pass through the dialytic membrane.In a recent randomized study of hemodialysis patients (30), we examined the effect of prolonged oral administration of dimercaptosuccinic acid (DMSA) 2.5 mg/kg per d compared with matching placebo. At 8 wk, there was no statistically significant difference in tHcy between placebo and DMSA. Subsequently, in vitro comparisons of a range of thiol agents led us to conclude that mesna (sodium 2-mercaptoethanesulfonic acid), a drug indicated to prevent hemorrhagic cystitis associated with ifosfamide chemotherapy, is a promising candidate. A dosage-finding pilot study was conducted in 10 hemodialysis patients to determine whether a single intravenous dose of 2.5 or 5.0 mg/kg mesna would lower tHcy (31). The results of that pilot study indicated that 5.0 mg/kg intravenous mesna rapidly and significantly decreased tHcy, because plasma levels were 21% lower with mesna than with placebo control (32). Furthermore, the residual effect of mesna on plasma tHcy was still significant 2 d later, before the next dialysis session, with plasma tHcy 2.3 μmol/L lower than placebo control. This suggested that routine 5.0 mg/kg mesna at the beginning of dialysis would have a cumulative effect and substantially decrease tHcy. Because a single dose of mesna administered in our pilot study caused a significant decrease in plasma tHcy, we designed this study to test the prolonged tHcy-lowering effect of 5.0 mg/kg mesna in a randomized, double-blind, placebo-controlled trial. The primary objective was to determine whether 5.0 mg/kg mesna at the commencement of each dialysis treatment thrice weekly for 8 wk would lower plasma tHcy while vigilantly monitoring for adverse effects.Although mesna is used routinely as an adjunct to chemotherapy, adverse effects associated with its regular use in patients with ESRD are unknown; therefore, adverse effects associated with mesna therapy were intensely monitored during this trial. According to the product monograph, the most frequently reported adverse effects of mesna use include headache, nausea, vomiting, and diarrhea, and some patients have an allergic reaction to mesna. Mesna has been shown to deplete plasma thiols such as tHcy and cysteine in patients who undergo concomitant chemotherapy (33). As such, one theoretical concern is depletion of the intracellular antioxidant glutathione, although studies have shown that mesna depletes plasma cysteine, an essential precursor of glutathione synthesis, without affecting leukocyte glutathione (34).  相似文献   

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己酮可可碱(PTX)可减轻高脂饮食大鼠脂肪性肝炎和肝纤维化的程度,但其作用机制尚未明确.目的:探讨PTX对非酒精性脂肪性肝炎(NASH)大鼠肝脏基因表达谱的影响.方法:24只Spragu-Dawley大鼠在高脂饮食4周后随机分为模型组(n=12)和PTX干预组(n=12,PTX每天100 mg/kg),并继续予高脂饮食;6只普通饮食饲养大鼠作为对照组.于实验第24周处死大鼠,应用含15 650条基因的大鼠U230A芯片检测肝脏基因表达的改变.结果:与模型组相比,PTX干预组共出现370条差异表达基因,其中模型组较对照组上调而PTX干预后下调的基因57条,主要包括炎症/免疫反应相关基因、细胞信号转导相关基因、细胞外基质和细胞黏附分子基因、代谢酶和生物转化相关基因、离子通道/运输蛋白基因等;模型组较对照组下调而PTX干预后上调的基因25条,其功能涉及细胞信号转导、脂质代谢、生物转化等.结论:PTX可能通过影响NASH大鼠肝脏多种结构和功能基因的表达而有助于NASH和肝纤维化的防治.  相似文献   

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Background

Maintenance of the adequate intraoperative renal perfusion is very important during Orthotopic Liver Transplantation (OLT) to prevent acute renal failure.

Objectives

For the first time, this study was designed to survey the effects of octreotide on urine output during anesthesia for OLT and early postoperative renal function.

Patients and Methods

In this randomized double-blind placebo controlled clinical trial, 79 of 89 patients who underwent OLT and fulfilled the study requirement were randomly allocated into two groups. In the octreotide group, the patients received octreotide infusion from the start of the operation. On the other hand, the control group patients received physiologic saline infusion instead of octreotide. The Mean Arterial Pressure (MAP), heart rate, urine output, norepinephrine usage, and dosage during the three stages of OLT, and baseline and postoperative creatinine were recorded and compared between the two groups.

Results

No significant differences were found between the two groups regarding the demographic characteristics and graft factors (P > 0.05). However, urine output and MAP during the three stages of OLT were significantly higher in the octreotide group compared to the control group (P < 0.05). Moreover, no significant difference was observed between the two groups regarding baseline as well as postoperative creatinine (P > 0.05).

Conclusions

The results demonstrated that octreotide infusion during anesthesia for OLT not only augmented the vasoconstriction effect of norepinephrine to increase MAP, but also maintained better renal perfusion and urine output during the operation.  相似文献   

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