[Show abstract][Hide abstract] ABSTRACT: 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.
[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: 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).
[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.
Expert review of gastroenterology & hepatology 05/2013; 7(4):361-4.
[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. · 6.18 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. · 1.66 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.
[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
[Show abstract][Hide abstract] ABSTRACT: Introduction. 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. Methods. Ninety-four HCV outpatients aged <60 years who met the criteria of nondiabetic, nonobese, noncirrhotic, and nonalcohol abusers were included and compared to 29 controls. Fasting glucose, insulin, adiponectin, and lipid profiles were determined. IR was estimated by HOMA-IR and HOMA-AD. Results. The groups were similar regarding sex and BMI, but the HCV patients were older. The median insulin level was higher in the HCV group (8.6 mU/mL (6.5-13.7) versus 6.5 (4.3-10.7), P = 0.004), as was median HOMA-IR (1.94 (1.51 to 3.48) versus 1.40 (1.02 to 2.36), P = 0.002) and the prevalence of IR (38.3% versus 10.3% (P = 0.009)). No differences were found in adiponectin levels (P = 0.294) and HOMA-AD (P = 0.393). Conclusion. IR is highly prevalent even in low-risk HCV outpatients. Adiponectin is not influenced by the presence of HCV. HOMA-AD does not seem to be useful in assessing IR in HCV patients.
International journal of hepatology. 01/2012; 2012:576584.
[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.
International journal of hepatology. 01/2012; 2012:698905.
[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 01/2012; 4(4):403-14.
[Show abstract][Hide abstract] ABSTRACT: Orthotopic liver transplantation (OLT) has been the standard treatment for end-stage acute and chronic liver disease. Ischemia-reperfusion (I/R) injury is one of the major causes of poor graft function early after OLT, and adversely influencing graft and patient survivals. It is unknown whether I/R injury influences liver fibrogenesis.
Livers from 25 adult male Wistar rats were randomly assigned into 5 experimental groups according to the preservation solution: saline solution (SS); University of Wisconsin (UW) solution; Fructose 1, 6-biphosphate (FBP); S-Nitroso-N-Acetylcysteine (SNAC): or UW+SNAC (SNAC+UW). Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactic dehydrogenase (LDH) were determined in preservation solution samples at 2, 4, and 6 hours. After 6 hours of cold ischemia, ex situ reperfusion was applied to the liver for 15 minutes. Serum AST, ALT, LDH, and renin levels were determined. Fresh liver slices were processed for histological studies, determination of thiobarbituric acid reactive substances, catalase, and glutathione, and expression of TGF-β1 and angiotensin II AT1 receptor.
AST was significantly lower during cold storage with UW than with the older media (P=.001); ALT was lower in the FBP group (P=.023) and LDH was lower in the FBP and SNAC groups (P=.007). After reperfusion, serum AST, ALT, LDH, and TBARS showed no significant differences among the groups. Catalase was significantly lower in the SS and FBP groups (P=.008 and P=.006, respectively). Compared with UW, glutathione concentrations were significantly higher in SS, FBP, and SNAC 200 (P=.004). Renin levels were significantly lower in the FBP group (P=.022). No histological signs of preservation injury were observed in the hepatic sample. No expressions were detected of TGF-β1 or AT1 receptor.
In this experimental model of early reperfusion injury, preservation changes related to higher levels of renin, which suggest its role in fibrogenesis. FBP was associated with lower renin levels than other solutions including UW.
[Show abstract][Hide abstract] ABSTRACT: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) share the same transmission routes. About 30% of HIV-positive patients are co-infected with HCV. Of the various HCV-related extrahepatic events, those involving the skin may be the first sign of infection.
To specify the skin presentations in patients co-infected with HIV and HCV (co-infected patients; CP) and compare them with those found in patients with HCV mono-infection (mono-infected patients; MP).
This was a cross-sectional study, in which the studied population consisted of MP and CP from a tertiary hospital in the South of Brazil, who underwent complete skin examination and laboratory tests.
In total, 201 patients were assessed, of whom 108 were CP, and 93 were MP. Pruritus tended to be more common in MP. MP also had significantly more dermatological conditions (mean of 5.2) than CP (mean of 4.5). In total, 104 different skin diseases were identified. There was a higher prevalence of infectious diseases and pigmentation disorders, such as verruca vulgaris and facial melasma, in CP, whereas trunk and facial telangiectasias, palmar erythema, and varicose veins were more common in MP.
We found a high prevalence of skin conditions both in MP and in CP; however, the patterns of the dermatological conditions were different. CP were found to have significantly fewer skin lesions than MP, but had a higher prevalence of infectious and pigmentation disorders. By contrast, vascular conditions were more common in MP.
Clinical and Experimental Dermatology 11/2011; 37(2):122-7. · 1.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nitric oxide (NO) has been shown to act as a potent antifibrogenic agent by decreasing myofibroblast differentiation. S-Nitroso-N-acetylcysteine (SNAC), a NO donor, attenuates liver fibrosis in rats, but the cellular and molecular mechanisms on liver myofibroblast-like phenotype still remain unknown. Here, we investigate the antifibrotic effects of SNAC on hepatic stellate cells, the major fibrogenic cell type in the liver. A murine GRX cell line was incubated with SNAC (100μM) or vehicle (control group) for 72h. Cell viability was measured by MTT colorimetric assay and the conversion of myofibroblast into quiescent fat-storing cell phenotype was evaluated by Oil-Red-O staining. TGFβ-1, TIMP-1, and MMP-13 levels were measure in the supernatant by ELISA. Profibrogenic- and fibrolytic-related gene expression was quantified using real-time qPCR. SNAC induced phenotype conversion of myofibroblast-like phenotype into quiescent cells. SNAC decreased gene and protein expression of TGFβ-1 and MMP-2 compared to control groups. Besides, SNAC down-regulated profibrogenic molecules and up-regulated MMP-13 gene expression, which plays a key role in the degradation of interstitial collagen in liver fibrosis. In conclusion, these findings demonstrate that SNAC efficiently can modulate the activation and functionality of murine hepatic stellate cells and could be considered as an antifibrotic treatment to human liver fibrosis.
[Show abstract][Hide abstract] ABSTRACT: Fructose 1,6-biphosphate (FBP) has been shown to exert therapeutic effects in models of ischemia-reperfusion in organs other than the liver. This study compared FBP and University of Wisconsin (UW) solution during cold storage and reperfusion, among mitochondria of adult male Wistar rat livers.
Adult male Wistar rats were assigned to two groups according to the preservation solution used; UW or FBP Aspartate transaminase (AST), alanine transferase (ALT); and lactic dehydrogenase (LDH) were measured in samples of the storage solution obtained at 2, 4 and 6 hours of preservation. After 6 hours of cold storage, we reperfused the liver, taking blood samples to measure AST, ALT, LDH, and throbarbituric acid reactive substances (TBARS). Hepatic fragments were processed for histologic analysis; for determinations of TBARS, catalase, and nitric oxide as well as for mitochondrial evaluation by infrared spectroscopy.
During cold preservation, levels of AST and LDH in the storage solution were lower among the FBP group, but after reperfusion, serum levels of AST, ALT, and LDH were higher in this group, as was catalase activity. TBARS and nitric oxide were comparable between the groups. In the UW group there was a higher amide I/amide II ratio than in the FBP group, suggesting an abnormal protein structure of the mitochondrial membrane. No signs of preservation injury were observed in any liver biopsy, but sinusoidal congestion was present in livers preserved with FBP.
FBP showed a protective effect for preservation during cold storage seeming to protect the mitochondrial membrane although it did not prevent reperfusion injury.
[Show abstract][Hide abstract] ABSTRACT: Ischemia-reperfusion (I/R) injury is among the major causes of poor graft function early after liver transplantation that adversely influences patient survival. A variety of mediators have been implicated in the pathogenesis of I/R vascular injury, including nitric oxide (NO). Because of the beneficial effects of NO during preconditioning and reperfusion, strategies to prevent or ameliorate I/R injury through the stimulation of hepatic NO production are an area of significant clinical interest. We evaluated the role of S-nitroso-N-acetylcysteine (SNAC) as an NO donor in the prevention of liver I/R injury in an animal model.
Adult male Wistar rats were randomly assigned to 3 experimental groups containing 5 animals each: the University of Wisconsin (UW) solution group; SNAC solution group; and SNAC-containing UW solution (SNAC+UW) group. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were determined in samples of the cold storage solution at 2, 4, and 6 hours of preservation. After 6 hours of cold storage, We applied a 15-minute reperfusion period. Thereafter, the reperfusion was interrupted with blood samples obtained to measure AST, ALT, LDH, and thiobarbituric acid reactive substances (TBARS). Hepatic fragments were processed for histologic analysis, and to determine of TBARS, catalase, and glutathione levels.
During cold preservation, AST and LDH were significantly lower among the SNAC than the UW group or the SNAC+UW group (P = .004 and P = .03, respectively). ALT was comparable among the groups (P = .3). After reperfusion, serum levels of AST, ALT, and LDH, as well as of hepatic TBARS and catalase showed no differences among the groups. Glutathione concentration was lower in the SNAC and SNAC+UW group (P < .001) compared with the UW group. We did not observe histologic signs of preservation injury.
The SNAC solution showed a greater protective effect to preserve rat livers during cold storage, but it was comparable with UW.