[Show abstract][Hide abstract] ABSTRACT: This study sought to determine the role of physical training (PT) on body weight (BW), energy balance, histological markers of nonalcoholic fatty liver disease (NAFLD) and metabolic gene expression in the liver of ob/ob mice. Adult male ob/ob mice were assigned into groups sedentary (S; n = 8) and trained (T; n = 9). PT consisted in running sessions of 60 min at 60% of maximal speed conducted five days per week for eight weeks. BW of S group was higher from the 4(th) to 8(th) week of PT compared to their own BW at the beginning of the experiment. PT decreased daily food intake and increased resting oxygen consumption and energy expenditure in T group. No difference was observed in respiratory exchange ratio, but the rates of carbohydrate and lipids oxidation, and maximal running capacity were greater in T than S group. Both groups showed liver steatosis but not inflammation. PT increased CPT1a and SREBP1c mRNA expression in T group, but did not change MTP, PPAR-α, PPAR-γ, and NFKB mRNA expression. In conclusion, PT prevented body weight gain in ob/ob mice by inducing negative energy balance and increased physical exercise tolerance. However, PT did not change inflammatory gene expression and failed to prevent liver steatosis possible due to an upregulation in the expression of SREBP1c transcription factor. These findings reveal that PT has positive effect on body weight control but not in the liver steatosis in a leptin deficiency condition.
International Journal of Clinical and Experimental Medicine 09/2015; 8(7):10911-9. · 1.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the survival rates after transarterial embolization (TAE).
One hundred third six hepatocellular carcinoma (HCC) patients [90 barcelona clinic liver cancer (BCLC) B] were submitted to TAE between August 2008 and December 2013 in a single center were retrospectively studied. TAE was performed via superselective catheterization followed by embolization with polyvinyl alcohol or microspheres. The date of the first embolization until death or the last follow-up date was used for the assessment of survival. The survival rates were calculated using the Kaplan-Meier method, and the groups were compared using the log-rank test.
The overall mean survival was 35.8 mo (95%CI: 25.1-52.0). The survival rates of the BCLC A patients (33.7%) were 98.9%, 79.0% and 58.0% at 12, 24 and 36 mo, respectively, and the mean survival was 38.1 mo (95%CI: 27.5-52.0). The survival rates of the BCLC B patients (66.2%) were 89.0%, 69.0% and 49.5% at 12, 24 and 36 mo, respectively, and the mean survival was 29.0 mo (95%CI: 17.2-34). The survival rates according to the BCLC B sub-staging showed significant differences between the groups, with mean survival rates in the B1, B2, B3 and B4 groups of 33.5 mo (95%CI: 32.8-34.3), 28.6 mo (95%CI: 27.5-29.8), 19.0 mo (95%CI: 17.2-20.9) and 13 mo, respectively (P = 0.013).
The BCLC sub-staging system could add additional prognosis information for post-embolization survival rates in HCC patients.
World Journal of Hepatology 03/2015; 7(3):628-32. DOI:10.4254/wjh.v7.i3.628
[Show abstract][Hide abstract] ABSTRACT: According to the current criteria, the diagnosis of early allograft dysfunction usually cannot be established before the end of the first week after liver transplantation. Thus, early predictive tests for detecting allograft dysfunction are still warranted to prevent allograft failure. This study was undertaken to assess the role of low serum factor V activity as an early prognostic factor (postoperative day 2) after liver transplantation.
A retrospective review of all consecutive adult patients who underwent first orthotopic whole-graft liver transplant at our institution between March 2002 and June 2011 was undertaken. Primary endpoint was graft failure within 90 days after transplantation.
Of all 105 patients analyzed in this study, 39 (37.1 %) were female and 66 (62.9 %) were male. Mean age was 52.7 ± 11.7 years, and median follow-up period was 2474 ± 164 days. There were overall 33 (31.4 %) deaths, 13 of those occurring on the first 90 post-transplant days. Multivariate analysis demonstrated that serum factor V lower than 41.5 % and female gender had a negative impact not only on allograft failure/death within 90 days after transplantation (RR = 5.30, CI = 1.40-20.2, p = 0.015 and RR = 5.23, CI = 1.53-21.33, p = 0.008) but also on overall mortality. For prediction of allograft failure/death occurring during the first 3 months, serum factor V level of 41.5 % or lower exhibited a specificity of 87.9 %, a sensitivity of 42.9 %, an accuracy of 81.9 %, a positive predictive value of 35.3 %, and a negative predictive value of 90.9 %.
Assessment of serum factor V levels on postoperative day 2 might be a promising prognostic tool for early prediction of inferior outcomes after liver transplantation.
Langenbeck s Archives of Surgery 02/2015; 400(5). DOI:10.1007/s00423-015-1290-2 · 2.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Transarterial chemoembolization (TACE) and transarterial embolization (TAE) have improved the survival rates of patients with unresectable hepatocellular carcinoma (HCC); however, the optimal TACE/TAE embolic agent has not yet been identified. The aim of this study was to compare the effect of two different embolic agents such as microspheres (ME) and polyvinyl alcohol (PVA) on survival, tumor response, and complications in patients with HCC submitted to transarterial embolization (TAE). Eighty HCC patients who underwent TAE between June 2008 and December 2012 at a single center were retrospectively studied. A total of 48 and 32 patients were treated with PVA and ME, respectively. There were no significant differences in survival (
) or tumoral response (
) between groups (PVA or ME). Overall survival rates at 12, 18, 24, 36, and 48 months were 97.9, 88.8, 78.9, 53.4, and 21.4% in the PVA-TAE group and 100, 92.9, 76.6, 58.8, and 58% in the ME-TAE group (
). Patients submitted to TAE with ME presented postembolization syndrome more frequently when compared with the PVA group (
). According to our cohort, the choice of ME or PVA as embolizing agent had no significant impact on overall survival.
[Show abstract][Hide abstract] ABSTRACT: Background/aims::
Nonalcoholic fatty liver disease (NAFLD) has emerged as an important cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). The Barcelona Clinic Liver Cancer (BCLC) system is the preferred staging system to evaluate patients with HCC and links prognosis assessment with treatment recommendation. The aim of this retrospective study was to evaluate whether the BCLC staging system and its treatment algorithm are suitable for patients with HCC arising from NAFLD.
Forty-two patients with HCC related to either to NAFLD or cryptogenic cirrhosis were retrieved retrospectively from 2 centers in Brazil. Patients were classified according to BCLC staging system. If the proposed HCC therapy could not be applied, the case was considered to represent deviations from the recommended BCLC guideline. Causes of treatment deviations were investigated.
There were 4 patients without evidence of cirrhosis according to liver biopsy and/or clinical evaluation. One (2%), 21 (50%), 10 (24%), 5 (12%), and 5 patients (12%) were classified initially to the very early (0), early (A), intermediate (B), advanced (C), and terminal (D) BCLC stages, respectively. Thirty-five patients (83%) were treated according to BCLC recommendations. There were 3 cases (of 5) of protocol deviation in BCLC C patients. The 1- and 2-year overall survival rates were 81% and 66%, respectively.
The BCLC system is applied in most cases of NAFLD-related HCC cases. Deviation of BCLC is found more frequently in BCLC C stage patients.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivitives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.
American Journal of Clinical Oncology 09/2014; DOI:10.1097/COC.0000000000000134 · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The mechanisms involved in organ protection by volatile anaesthetics are not completely understood. In the liver transplant setting, there is a lack of information in the literature about whether sevoflurane anaesthesia has a superior hepatoprotective effect when compared with isoflurane.
European Journal of Anaesthesiology 08/2014; 31(12). DOI:10.1097/EJA.0000000000000127 · 2.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: & Aims: Transient elastometry is a non-invasive procedure used to measure fibrosis when patients are diagnosed with liver disease; it might be used to monitor changes over time. We investigated whether there are short-term variations in stiffness measurements not attributable to changes in fibrosis by studying patients with stable liver disease.
[Show abstract][Hide abstract] ABSTRACT: Background and aims:
Spontaneous bacterial peritonitis (SBP) often triggers acute-on-chronic liver failure (ACLF). Acute kidney injury (AKI) is frequent and correlates with higher mortality in such cases. The aim of this study is to evaluate the Acute Kidney Injury Network (AKIN) criteria in the prediction of death in cirrhotic patients after an episode of SBP.
Material and methods:
Forty-six cirrhotic patients with SBP were included in a cohort study. Renal injury was estimated by AKIN criteria (grades 1, 2 or 3) to examine the association between AKI severity and mortality. Patients were followed-up for a mean of 13.22 months. Kaplan-Meier survival curve and the hazard ratio of mortality by Cox regression model were calculated accordingly to the AKIN criteria.
The mean age of the included patients was 56.94 ± 9.49; 29 (63%) were male. Mean MELD score was 19.46 ± 6.16; 78.3% were Child-Pugh C. AKI occurred in 43.5% of patients (8.7, 17.4 and 17.4% respectively for AKIN criteria 1, 2 and 3). Inpatient mortality for AKIN 1, 2 and 3 was 50, 37.5 and 62.5 vs. 3.8% for patients without renal injury (p = 0.002, 0.001 and < 0.001 respectively). Patients with AKIN grades 1, 2 or 3 had no significant differences regarding MELD score (p = 0.893). The hazard ratio and 95% confidence interval of mortality for patients with AKI (AKIN grades 1, 2 and 3 grouped) were 3.41 (1.58-7.36).
AKIN criteria are useful to predict mortality in patients with SBP.
Annals of hepatology: official journal of the Mexican Association of Hepatology 04/2014; 13(3):390-5. · 2.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Minimal hepatic encephalopathy (MHE) is common in cirrhotic. Its optimal treatment is still under investigation.
To assess efficacy/safety of oral l-ornithine-l-aspartate (LOLA) in controlling MHE.
Consecutive cirrhotic outpatients with MHE - psychometric tests (PHES) - NCT-A/B and DSST> 2 standard deviation, were randomized to 60-day oral LOLA (5g t.i.d) or placebo. Critical Flicker test (CFF), quantitative EEG (qEEG), arterial ammonia (NH3), Beck's anxiety-depression forms and LD-QOL were assessed. Patients were followed by 6 months after the end of the study to assess LOLA prophylactic role on overt hepatic encephalopathy (OHE).
64 patients were included - 63 (98.4%) with MHE. In 6/63 CFF was <39Hz (9.52%); NH3 was increased in 32 (50.8%); 25% had abnormal qEEG. Age, sex, scholarship, Child-Pugh (CP), MELD, NCT-A/B, DSST, CFF and NH3 were similar in both groups at the baseline. LOLA led to a significant improvement in NCT-B age-controlled z-score (3.4 ± 3.4 vs. 1.5 ± 2.3 - P=0.01) and CFF (42.2 ± 5.8 vs. 45.2 ± 5.8 - P=0.02), comparing the first and the last visit, but there were no differences between LOLA and placebo regarding the whole PHES battery, CFF, LD-QOL and Beck's forms. No serious adverse effects occurred. Patients taking LOLA had fewer episodes of OHE at 6-month (5% vs. 37.9% - P=0.016), as they have significant improvement on liver function assessed by CP (P<0.001).
A 60-day oral LOLA course was not better than placebo on treating MHE, but was useful on preventing further episodes of OHE. Clinical Trials (NCT-00896831).
Hepatology Research 09/2013; 44(9). DOI:10.1111/hepr.12235 · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Liver transplantation is the standard of care for acute and chronic end-stage liver disease. Advances in medical therapy and surgical techniques have transformed the long-term survival of liver-transplant (LT) recipients. The prevalence of post-transplant cardiovascular complications has been rising with increased life expectancy after liver transplantation. Currently, deaths related to cardiovascular complications are one of the main causes of long-term mortality in LT recipients, as cardiovascular disease is the reason of 19-42% of non-liver-related mortality after transplant. On the other hand, metabolic syndrome is common among LT recipients before and after transplantation. In fact, their components (abdominal obesity, diabetes mellitus, hypertension and dyslipidemia) are often exacerbated by transplant-specific factors, such as immunosuppression, inappropriate diet, smoking and a sedentary lifestyle, and add a significant risk of developing atherosclerosis. These aspects are discussed in this article.
[Show abstract][Hide abstract] ABSTRACT: The role of hepatitis C virus (HCV) in the pathogenesis of atherosclerosis and cardiovascular events is unclear. The aim of this study was to evaluate the direct effect of HCV on cardiovascular risk and correlate it with pro and anti-inflammatory cytokines in patients with HCV. HCV monoinfected patients, genotype 1, naive, non-obese (BMI<30) and non-diabetics were included and compared to controls (blood donors). Patients with prior diagnosis of cardiovascular diseases, hypertension, chronic renal failure, cancer and chronic use of lipid-lowering drugs or immunosuppressants were excluded. Age, BMI, systolic blood pressure (SBP) and diastolic (DBP), fasting glucose and lipid levels were determined. Serum cytokines (IL-6, IL-10 and TNF-α) and Framingham score were also evaluated. 62 HCV patients, 34 (54.8%) were males and none of them was smoking. The Framingham scores (median and 25th and 75th percentiles) were 12% (6.5-14%), showing an intermediate cardiovascular risk in patients with HCV. There was significant direct correlation between Framingham and total cholesterol (p=0.043) and DBP (p=0.007). HDL-C (p=0.002) was inversely correlated with the Framingham score. HCV patients had higher levels of proinflammatory cytokines (IL-6 and TNF-α) compared to controls (p<0.0001) and the relation of proinflammatory/anti-inflammatory TNF-α/IL10 and IL-6/IL10 were higher in HCV patients (p<0.01). The Framingham score was directly correlated to IL-6 and TNF-α, but differences were not statistically significant. Patients with HCV monoinfected, nonobese, naïve and non diabetic have an intermediate cardiovascular risk, as measured by the Framingham score and high levels of proinflammatory cytokines (IL-6 and TNF).
International journal of cardiology 04/2013; 164(2):221-226. DOI:10.1016/j.ijcard.2011.07.016 · 4.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Various ocular lesions are associated with hepatitis C virus (HCV). Few studies have focused on untreated patients. This study aims to describe ocular lesions in untreated HCV-infected patients without ophthalmic symptoms by means of a comprehensive ophthalmologic examination.
Ninety-five consecutive naive HCV chronically infected patients and 54 controls (blood donors) were enrolled in a prospective, cross-sectional, single-center study. The following variables were analyzed: age, sex, HCV viral load and genotype, liver fibrosis, visual acuity, biomicroscopy of the anterior segment, lacrimal function (tear break-up time) and Schirmer's tests), posterior segment examination, and intraocular pressure.
HCV-infected patients presented an almost four times higher risk of lacrimal function involvement by tear break-up time [odds ratio (OR)=3.76; 95% confidence interval (CI) 1.75-8.04, P=0.001] and Schirmer's test (OR=4.17; 95% CI 1.83-9.50, P=0.001) than the controls. The chances of palpebral biomicroscopic lesions (blepharitis) were also higher (OR=3.21; 95% CI 1.49-6.94, P=0.003). Mean tonometry was higher in HCV patients (right eye 14.4±2.3 vs. 12.2±1.5, P<0.001 and left eye 14.5±2.3 vs. 12.0±1.4, P<0.001).
Naive HCV patients even with no ophthalmic complaints presented a greater prevalence of lacrimal function abnormalities and a higher frequency of blepharitis compared with the control group. As never formerly described, intraocular pressure in HCV patients was higher than that in controls.
European journal of gastroenterology & hepatology 04/2013; 25(4):411-5. DOI:10.1097/MEG.0b013e32835bc2f1 · 2.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Protein-calorie malnutrition (PCM) is a prognostic factor increasing complications and mortality in chronic liver diseases. Objectives: To quantify the dietary intake and compare different methods of nutritional assessment in patients with chronic liver diseases. Ninety seven outpatients of Hospital de Clínicas de Porto Alegre, with chronic hepatits (CH) and cirrhosis (CIR), were assessed from April 2009 to January 2010. The CH patients presented higher calorie and protein intake (p<0.05) than the CIR patients. Malnutrition prevalence in CH and CIR groups by the Royal Free Hospital-Global Assessment (RFH) was 51.2 vs 84%, Hand Grip Strength 61 vs 82.1%, Subjective Global Assessment 14.6 vs 32.1%, Adductor Pollices Muscle 7.3 vs 14.3%, Arm Muscle Circumference 4.9 vs 14.3% and Body Mass Index2.4 vs 3.6% (p<0.05), respectively. HGS and RFH were the best methods to identify malnutrition and present concordance with each other.
Revista Chilena de Nutricion 12/2012; 39(4):152-158. DOI:10.4067/S0717-75182012000400007
[Show abstract][Hide abstract] ABSTRACT: To investigate whether increased levels of vimentin citrullinated peptides identified by MS in articular cartilage can be measured in pathologies other than rheumatoid arthritis and be utilised for diagnostic purposes.
A monoclonal antibody against the sequence RLRSSVPGV-citrulline (VICM) was developed and evaluated in a carbon tetrachloride (CCl(4)) (n=52 + 28 controls) rat model of liver fibrosis and two clinical cohorts of adult patients with hepatitis C (HCV) (n=92) and non-alcoholic fatty liver disease (NAFLD) (n=62), and compared to healthy controls.
In CCl(4)-treated rats, mean systemic VICM levels increased 31% at week 12 (176 ng/mL, P<0.001), 41.7% at weeks 16 (190 ng/mL, P<0.001), 49.2% at weeks 20 (200 ng/ml, P<0.001), compared to controls (134 ng/mL). VICM levels correlated with total hepatic collagen determined by Sirius red staining of rat livers (r=0.75, P<0.05). In the HCV cohort, when stratified according to the METAVIR F score, VICM levels were 63% higher in F0 (632 ng/mL ±75, p<0.05), 54% in F1 (597 ng/mL ±41.3, p<0.05) and 62% in F2 (628 ng/mL ±59, p<0.05) all compared to controls. In the NAFLD cohort, VICM levels were 20.6% higher in F0 (339 ±12 ng/mL, P<0.05), 23.8% in F1 (348 ±12 ng/mL, P<0.05) and 28.8% in F2 (362 ±25 P<0.05).
We demonstrated increased serological levels of citrullinated and MMP degraded vimentin in an animal model of liver fibrosis and in early fibrosis associated with HCV and NAFLD patients. These data suggest that citrullinated and MMP degraded proteins are also present in liver fibrosis.
American Journal of Translational Research 11/2012; 4(4):403-14. · 3.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: . There is an association between HCV and insulin resistance (IR), which is currently assessed by HOMA-IR. There is evidence that HOMA-adiponectin (HOMA-AD) is more accurate, but its role in HCV patients is unknown. The purpose of this study was to evaluate IR in an HCV sample and controls, in order to compare the accuracy of HOMA-IR and HOMA-AD.
. Ninety-four HCV outpatients aged
[Show abstract][Hide abstract] ABSTRACT: Aims. To determine lymphocyte IRS (IRS1 cells) in HCV patients, correlating it to liver IRS (IRS 1liver) and HOMA-IR. This study tested the hypothesis that IRS1 cells expression can be used as insulin resistance (IR) marker in HCV-infected patients. IRS1 cells were not studied before in HCV infection. Materials and Methods. HCV chronically infected patients, naïve, nonobese, noncirrhotic, and nondiabetic were prospectively included and compared to controls (blood donors). Blood was taken, and leukocytes were separated. IRS1 was determined by real-time PCR. Liver tissue was obtained from transplant donors as controls. Results. 41 HCV-positive patients were included, 26 males (60.5%); mean age of 45 (±7.9); 33 (80.5%) from genotype 1. 6 out of 12 controls were males (50%); mean age was 26.7 (±3.2). There was expression of IRS1 in leukocytes. The median IRS1 cells (HCV) were 0.061 (0.004 to 0.469); the median IRS 1liver (HCV) was 0.0003 (0.00002 to 0.0186)-lower than in controls (resp., P = 0.005 and P = 0.018). HOMA-IR had an inverse correlation with IRS 1liver (P = 0.04). There was no correlation between IRS1 liver and IRS1 cells (P = 0.930). Conclusions. There was expression of IRS1 in leukocytes. IRS1 cells and IRS1 liver were lower in HCV patients than in controls.
[Show abstract][Hide abstract] ABSTRACT: Background and Aims: Cardiovascular events are increasing in
LTR. Leukocyte and vascular adhesion molecules (CAMs) such
as selectins, VCAM-1, and ICAM-1 play a critical role in the
development of atherosclerosis. We investigated conventional and
novel cardiovascular biomarkers (CB) in LTR.
Methods: 95 patients were submitted to liver transplant between
August 2009 and July 2010, and followed-up by 1 year. 42
were consecutively included and compared to patients with
biopsy proven NASH (n = 19) and lean (BMI <30) controls (n = 10).
Features of metabolic syndrome, glucose and lipid profile, HOMAIR,
cardiovascular biomarkers and inflammatory cytokines were
determined.Results: When compared to NASH patients, LTR had a significantly
lower BMI (24.4±4.32 vs 31.7±4.35 – P < 0.001), age (P < 0.001), AST
(P = 0.002), ALT (P < 0.001), fasting glucose (P < 0.001), fasting insulin
(P = 0.03), and HOMA-IR (2.65 [1.68–4.27] vs 5.02 [3.62–6.7] –
P < 0.001). However, they did not differ regarding total cholesterol,
HDL and LDL-cholesterol, triglycerides and blood pressure. Table
shows CB results.
Cardiovascular biomarkers results
Variable NASH (n = 19) LTR (n = 42) Controls (n = 10) P
VCAM1 1692.4±457.4 1820.6±443.9 1167.2±121.8 <0.001
ICAM1 259.7±101 230.3±96.3 152.9±33.9 0.015
E-selectin 90.03 (69.5–137.1) 48.5 (36.04–70.9) 35.7 (28.4–47.04) <0.001
In LTR there were a significant correlation between ICAM1 and
VCAM1 (P = 0.03), and also among ICAM1 and e-selectin (P = 0.02)
and e-selectin and adiponectin (P = 0.02). There were no correlation
among CAMs and BMI, lipid or glucose profile. There were a
significant inverse correlation among ICAM1, VCAM1 and IL-10
(P = 0.02 and 0.03, respectively). CRP and PAI-1, conventional CB,
were not increased in LTR.
Conclusions: After a short 1-year follow-up, LTR, even younger
and lighter than NASH patients, and with no significant insulin
resistance or CRP and PAI-1 elevation, had a similar increase of
early CB (CAMs) like a notorious high risk NASH population. These
results emphasize that LTR are under elevated risk of cardiovascular
events and need to be early screened.
47th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL); 04/2012