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Introduction: The intermediate stage of the Barcelona Clinic Liver Cancer (BCLC) classification includes a heterogenous population of patients with hepatocellular carcinoma (HCC), and palliative treatment with transarterial chemoembolization is recommended for all of them. In this regard, 2 other classifications could be useful, the subclassification BCLC-B (SUB) and the classification Hong Kong Liver Cancer (HKLC)., Objective: To determine the indication of curative or palliative treatment between SUB and HKLC in BCLC-B patients., Patients and Methods: A retrospective study in HCC patients seen between 2011 and 2016 in southern Brazil. Demographic, clinical, and laboratory data were collected. HCC staging was performed with BCLC, SUB, and HKLC., Results: A total of 570 patients with HCC were assessed, of whom 95 were classified as BCLC-B: 25 (26.0%) B1, 48 (50.5%) B2, 9 (9.5%) B3, and 13 (13.7%) B4. Overall median survival was 21.1 (95% confidence interval, 14.2-28.0) months. Median survival was higher for BCLC-B1 patients than in subgroups B3 (P=0.046) and B4 (P=0.001), and this was also seen for B2 versus B4 (P=0.044). Regarding the HKLC classification, a significantly higher median survival was observed for HKLC-I and HKLC-IIB in relation to the categories HKLC-IIIA (P<0.001 and 0.004, respectively) and HKLC-IIIB (P<0.001 and 0.006, respectively). When HKLC was applied, the following were identified as candidates for curative treatment: BCLC-B1, 24 (96.0%); BCLC-B2, 26 (54.2%); BCLC-B3, 0 (0%); and BCLC-B4, 3 (23.1%)., Conclusion: In intermediate HCC, SUB was able to identify a subset of patients with a higher overall survival. According to HKLC, 55.8% of BCLC-B patients could receive curative treatment.

Background: Cardiovascular disease is a major cause of death in post-liver transplantation (LT). The aim of this study was to evaluate LT patients as to the carotid intima-media thickness (CIMT) and its association with nutritional status, dietary intake, metabolic profile and cardiovascular risk factors., Methods: In this cross-sectional study, adult patients with more than 12 months of post-transplant follow-up underwent clinical, laboratory, functional and nutritional evaluation by 3-day-diet-record, anthropometry and dynamometry. CIMT was evaluated by Doppler ultrasonography., Results: Sixty-nine post-LT patients [males 61%, median of age 59 (51-64) years were included; median time post-liver transplantation 2.8 (1.4-6.3) years]. High prevalence of malnutrition was found (45% of arm muscle area < p15 and 71% of handgrip strength < p30). Excess weight was present in 72% of patients, body mass index ≥ 30 kg/m 2 in 35% and metabolic syndrome in 51%. Abnormal CIMT was found in 54% of the sample. Patients with abnormal CIMT presented higher cardiovascular risk Score, LDL cholesterol, higher prevalence of high-sensitive C-reactive protein ≥ 1 mg/L and higher intake of saturated and trans fatty acids (P < 0.05 for all)., Conclusions: Abnormal IMT was commonly found in LT patients presenting at the same time with overweight and dynapemia. These results were associated with higher LDL-cholesterol levels, high-sensitive C-reactive protein ≥ 1 mg/L and higher intake of saturated and trans fatty acids. Preventive measures, including dietary advice, are required for all post-liver transplantation patients to minimize cardiovascular risk., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Liver cancer ranks fifth in incidence and fourth in overall cancer-related mortality, with approximately 854,000 new cases and 810,000 deaths per year worldwide. Hepatocellular carcinoma (HCC) accounts for 90% of these cases, and, over time, both the incidence and mortality of this cancer have been rising in many regions. Several staging systems are used to assess the extent of primary tumor, presence of metastasis, and underlying liver disease, and thereby aid in the definition of treatment strategies and prognosis for these patients. The consequence of this heterogeneity in HCC staging is that no consensual definition of advanced disease exists, and there is still ongoing debate on the optimal treatment for these patients. Patients with advanced tumors can be candidates for multiple therapies, ranging from potentially curative options such as transplantation and resection-to locoregional and systemic treatments; these should be evaluated on an individual basis by a multidisciplinary team. This paper provides an overview of treatment options for advanced stage HCC, based on a review of the latest relevant literature and the personal experience of the authors., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare.

Background: Hepatitis C is an important health problem. In Brazil, 1-2 million people are infected. Despite this expressive number, and the availability of very successful treatment, many patients remained undiagnosed mainly because of the asymptomatic nature of the infection., Objectives: To describe epidemiological characteristics of HCV-infected patients seen at referral centers in Brazil, the source of referral, and the time spanned to reach a reference center, in order to improve the identification of undiagnosed patients., Methods: Multicenter observational, cross-sectional study carried out in 15 centers of Brazil, between January/2016 and June/2017. Data of patients with a confirmed diagnosis (anti-HCV and HCV-RNA) were collected by interview using standard questionnaires and by review of charts., Results: Two thousand patients were included; 55.1% were male, mean age 58±11 years. Only 14.9% had higher education and 84.2% received up to five monthly minimum Brazilian wages (approximately US$260.00/month). The time between diagnosis and beginning of follow-up was 22.9 months. The most common reasons for testing were check-up (33.2%) and blood donation (19%). General practitioners diagnosed most of the patients (30.1%). Fibrosis stage was mainly evaluated by liver biopsy (61.5%) and 31.3% of the patients were cirrhotic at diagnosis., Conclusions: This multicenter Brazilian study showed that the mean time to reach a referral center for treatment was almost two years. Primary care physicians diagnoses most hepatitis C cases in the country. Population campaigns and medical education should be encouraged to intensify screening of asymptomatic individuals, considering the efficiency of check-ups in identifying new patients., (Copyright © 2019 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction and Aim: Approximately 650,000 people in Brazil have chronic hepatitis C virus (HCV) infection. We evaluated the safety and efficacy of ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) plus dasabuvir (DSV) with/without ribavirin (RBV) in an openlabel multicenter phase 3b trial in treatment-naive or interferon (IFN) treatment-experienced Brazilian patients with advanced hepatic fibrosis (METAVIR F3/4) and HCV genotype (GT) 1 infection., Material and Methods: All patients received coformulated OBV/PTV/r daily + DSV twice daily (3-DAA). GT1a-infected patients received 3-DAA plus RBV for 12 weeks, except for prior pegIFN/RBV nonresponders with cirrhosis who were treated for 24 weeks. GT1b-infected patients received 3-DAA alone (F3) or in combination with RBV (F4) for 12 weeks. The primary endpoint was sustained virologic response (HCV RNA &lt; 15 IU/mL) at post-treatment Week 12 (SVR12)., Results: The study enrolled 222 patients, 214 achieved an SVR12 (96.4%; 95% CI, 93.1-98.2%), one GT1a-infected patient experienced virologic breakthrough, six (5 GT1a) relapsed, and one was lost to follow-up. SVR12 was achieved in 111/ 112 (99.1%) GT1b-infected patients, including 42/43 (97.7%) noncirrhotic, and 69/69 (100%) cirrhotic patients; and in 103/110 (93.6%) GT1a-infected patients, including 44/46 (95.7%) noncirrhotic and 59/64 (92.2%) cirrhotic patients. Overall there was a low rate of serious adverse events (n = 6, 2.7%). One patient experienced a treatment-related serious adverse event and one patient discontinued treatment because of an adverse event., Discussion: The results confirm that the 3-DAA regimen with/without RBV is well tolerated and had a favorable safety profile and is efficacious in GT1-infected patients with advanced fibrosis (METAVIR F3/4).

Objective: The aim is assess, compare, and correlate maximal oxygen consumption (VO 2max. ), functional capacity and quality of life in cirrhotic patients with hepatitis C virus (HCV) and in healthy individuals., Methods: This case-control study included 36 participants (18 patients with HCV cirrhosis and 18 healthy individuals) matched for sex and age. VO 2max was assessed using ergospirometry with an incremental load test on a cycloergometer. Functional capacity was measured by a 6-min walk test (6WT), and quality of life was assessed using the 36-Item Short-Form Health Survey (SF-36)., Results: Both the cirrhotic group and the control group had similar results for sex (44.4% male) and age (55.6 ± 8.31 and 55.2 ± 8.85 years, respectively). The cirrhotic group scored lower in all domains of the SF-36, on the VO 2max test (cirrhotic group 16.2 [11.6-18.6] ml/kg/min; control group 19.9 [16.28-26.9]; p = 0.007) and on the 6WT (cirrhotic group 521.5 [476.25-544.75] m; control group 618.0 [570.75-643.75] m; p = 0.0001). Correlations were found between the 6WT and the VO 2max (r = 0.801, p < 0.0001) and between the 6WT and quality of life (SF-361-functional capacity domain; r = 0.552, p = 0.018) only in the cirrhotic group., Conclusion: Patients with cirrhosis due to HCV show changes in VO 2max and in functional capacity, which have a significant impact on their quality of life., (© 2018 John Wiley & Sons, Ltd.)

Background: Infection by hepatitis C virus is one of the leading causes of chronic hepatitis C and cause severe burden for patients, families and the health care system., Objective: The aims of this research were to assess the severity of liver fibrosis, comorbidities and complications of hepatitis C virus; to examine health-related quality of life (HRQoL), productivity loss and resource use and costs in a sample of Brazilian chronic hepatitis C, genotype 1, patients., Methods: This was a cross-sectional multicenter study performed in genotype-1 chronic hepatitis C patients to assess disease burden in the Brazilian public health care system between November 2014 and March 2015. Patients were submitted to a liver transient elastography (FibroScan) to assess liver fibrosis and answered an interview composed by a questionnaire specifically developed for the study and three standardized questionnaires: EQ-5D-3L, HCV-PRO and WPAI:HepC., Results: There were 313 subjects enrolled, with predominance of women (50.8%), caucasian/white (55.9%) and employed individuals (39.9%). Mean age was 56 (SD=10.4) years old. Moreover, 42.8% of patients who underwent FibroScan were cirrhotic; the most frequent comorbidity was cardiovascular disease (62.6%) and the most frequent complication was esophageal varices (54.5%). The results also showed that "pain and discomfort" was the most affected HRQoL dimension (55.0% of patients reported some problems) and that the mean HCV-PRO overall score was 69.1 (SD=24.2). Regarding productivity loss, the most affected WPAI:HepC component was daily activity (23.5%) and among employed patients, presenteeism was more frequent than absenteeism (18.5% vs 6.5%). The direct medical costs in this chronic hepatitis C sample was 12,305.72USD per patient in the 2 years study period; drug treatment costs represented 95.9% of this total., Conclusion: This study showed that most patients are cirrhotic, present high prevalence of cardiometabolic diseases and esophageal varices, reduced HRQoL mainly in terms of pain/discomfort, and work productivity impairment, especially presenteeism. Additionally, we demonstrated that hepatitis C virus imposes an economic burden on Brazilian Health Care System and that most of this cost is due to drug treatment.

Introduction: Occidental diet and metabolic profile seems to increase hepatic fibrosis (HF) in patients with chronic hepatitis C virus (HCV) infection, but there is scarce information about the diet components and their role in this setting., Objectives: This study aims to evaluate the dietary intake, metabolic profile, presence of metabolic syndrome (MetS) and cardiovascular risk in patients with chronic HCV infection according to the presence of fibrosis., Methods: Cross-sectional study which 58 patients with HCV infection without active antiviral therapy and non-cirrhotic were assessed. All patients were subjected to clinical, laboratorial and dietary evaluation, and classified according to the METAVIR score. Patients were divided as the presence of hepatic fibrosis., Results: In this sample, fifty-five percent of patients were females, the average age was 51.6 ± 9.7 years, and 79.3% were carriers of HCV genotype 1. Patients with HF presented higher energy, and fat intake as well as higher glycemic load of meals in comparison to those without HF. Patients with HF presented higher systolic and diastolic arterial pressure and higher levels of insulin., Conclusions: In conclusion, patients with HF had higher total daily energy and total fat intakes, and worse metabolic profile, characterized by a higher insulin resistance and blood pressure.

Introduction: Sorafenib (SOR) has proved to be effective in patients with advanced hepatocellular carcinoma (HCC), since overall survival was higher in phase III clinical trials; however, disease progression can occur., Objectives: The study aimed to describe real-life experience in advanced HCC treatment with SOR at a university hospital in Brazil and to estimate the number of patients with indication of second-line therapy., Methods: This is a retrospective study that included cases of HCC with prescription of SOR based on real-life practice between 2011 and 2016. Demographic, clinical, and laboratory data were collected., Results: From 572 patients with HCC, SOR was prescribed in 103 cases. From them, 62.1% were classified as Child-Pugh (CP)-A, 54.4% as Barcelona Clinic Liver Cancer (BCLC)-C, and 74 (71.8%) started treatment. Overall survival was 25.5 (95% CI 17.0-34.1) months and 1-year survival was greater in patients who received SOR than in non-treated (88.7 vs. 44.4%, p < 0.001). There was no difference in survival between BCLC-B and C (p = 0.405), as well as CP-A and B (p = 0.919). In 21.6% of the patients, a second-line therapy with regorafenib was indicated., Conclusion: In this real-life study, SOR significantly increased the survival rate by 1 year in patients with advanced HCC regardless of BCLC staging and CP score. Second-line therapy would be indicated in 21.6% of cases., (© 2018 S. Karger AG, Basel.)

Vitamin D deficiency is prevalent in liver disease and vitamin D has been shown to decrease hepatic fibrosis through an anti-TGFβ-1/SMAD3 effect mediated by the vitamin D receptor. Thus, we hypothesized that genetic variants involved in vitamin D metabolism and/or VDR/TGFβ-1/SMAD3 interaction could impact on the progression of chronic HCV. We obtained or imputed genotypes for 40 single nucleotide polymorphisms (SNPs) located in genes implicated in vitamin D metabolism from the HALT-C cohort via dbGaP. The HALT-C study followed 692 chronic HCV patients over 4 years, evaluating clinical outcomes including worsening of fibrosis, hepatic decompensation (gastric/esophageal bleeding, CTP>7, ascites, spontaneous bacterial peritonitis and encephalopathy), development of hepatocellular carcinoma, and liver death. We tested the selected SNPs for association with these outcomes in 681 HALT-C subjects. Eleven SNPs presented tendency towards significance (P<0.05): four SNPs in DHCR7 related to with hepatic decompensation (rs4944957, rs12800438, rs3829251 and rs4945008); two in GC to worsening of fibrosis and liver death (rs7041 and rs222020); two in CYP2R1 to ascites and hepatocellular carcinoma (rs7116978 and rs1562902); two in VDR to gastric/esophageal bleeding and hepatocellular carcinoma (rs4516035 and rs2239186); and one in SMAD3 to worsening of fibrosis and encephalopathy (rs2118610). Only rs1800469 in TGFB1 was statistically associated with hepatic decompensation after Bonferroni's correction (P<0.00125). In conclusion, rs1800469 in TGFB1 was associated to hepatic decompensation in chronic hepatitis C, while the other 11 described polymorphisms must be evaluated in a larger cohort to determine the possible role of vitamin D in hepatitis C.

Introduction and Aim: Vitamin D has been associated with chronic liver diseases and low vitamin levels may contribute to progression of chronic hepatitis C. The aim of this study was to evaluate the influence of vitamin D serum levels and GC gene polymorphisms in the severity of liver fibrosis in patients with chronic hepatitis C genotype 1., Material and Methods: Cross-sectional study that enrolled 132 adult patients with chronic hepatitis C genotype 1 attended at the outpatient Clinic of Gastroenterology Division at Hospital de Clínicas de Porto Alegre. At the time of enrollment patients had a blood withdraw for serum 25(OH)D determination and genotypic analysis of rs7041 and rs4588 polymorphisms in GC gene. None/mild fibrosis was considered as METAVIR F0, F1 and F2 and severe fibrosis as METAVIR F3 and F4., Results: Median 25(OH)D levels in the sample were 19.9 ng/mL (P25-P75: 14.0-29.4). Fifty percent of patients presented vitamin D deficiency (< 20 ng/mL). In stepwise multiple linear regression the variables associated with 25(OH)D levels were blood withdrawn in Winter/spring season, the haplotypes AT/AT + AG/AT of rs7041 and rs4588 and female sex. For evaluation of severe fibrosis, variables associated in logistic regression were age, vitamin D severe deficiency (< 10 ng/mL), glucose levels, BMI and platelets count., Conclusions: Vitamin D levels are associated with severity of liver fibrosis in chronic hepatitis C genotype 1 patients. Although the rs7041 and rs4588 GC polymorphisms are strong predictors of vitamin D levels, they do not play a direct role in liver fibrosis.

Background: Reliable measurement of basal energy expenditure (BEE) in liver transplant (LT) recipients is necessary for adapting energy requirements, improving nutritional status and preventing weight gain. Indirect calorimetry (IC) is the gold standard for measuring BEE. However, BEE may be estimated through alternative methods, including electrical bioimpedance (BI), Harris-Benedict Equation (HBE), and Mifflin-St. Jeor Equation (MSJ) that carry easier applicability and lower cost., Aim: To determine which of the three alternative methods for BEE estimation (HBE, BI and MSJ) would provide most reliable BEE estimation in LT recipients., Methods: Prospective cross-sectional study including dyslipidemic LT recipients in follow-up at a 735-bed tertiary referral university hospital. Comparisons of BEE measured through IC to BEE estimated through each of the three alternative methods (HBE, BI and MSJ) were performed using Bland-Altman method and Wilcoxon Rank Sum test., Results: Forty-five patients were included, aged 58±10 years. BEE measured using IC was 1664±319 kcal for males, and 1409±221 kcal for females. Average difference between BEE measured by IC (1534±300 kcal) and BI (1584±377 kcal) was +50 kcal (p=0.0384). Average difference between the BEE measured using IC (1534±300 kcal) and MSJ (1479.6±375 kcal) was -55 kcal (p=0.16). Average difference between BEE values measured by IC (1534±300 kcal) and HBE (1521±283 kcal) was -13 kcal (p=0.326). Difference between BEE estimated through IC and HBE was less than 100 kcal for 39 of all 43patients., Conclusions: Among the three alternative methods, HBE was the most reliable for estimating BEE in LT recipients., Competing Interests: none

Background: Topical hypothermia (TH) and ischemic preconditioning (IPC) are used to decrease I/R injury. The efficacy of isolated or combined use of TH and IPC in the liver regarding inflammation and cytoprotection in early ischemia/reperfusion (I/R) injury needs to be evaluated., Material and Methods: Wistar rats underwent 70% liver ischemia for 90 min followed by 120 min of reperfusion. Livers of animals allocated in the sham, normothermic ischemia (NI), IPC, TH, and TH+IPC groups were collected for molecular analyses by ELISA and Western blot, aiming to compare proinflammatory, anti-inflammatory, and antioxidant profiles., Results: Compared with NI, TH presented decreased tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-12 concentrations and increased IL-10 levels. TH animals displayed lower inducible nitric oxide synthase (iNOS) and higher endothelial nitric oxide synthase (eNOS) expressions. NAD(P)H-quinone oxidoreductase-1(NQO1) expression was also lower with TH. Isolated IPC and NI were similar regarding all these markers. TH+IPC was associated with decreased IL-12 concentration and reduced iNOS and NQO1 expressions, similarly to isolated TH. Expression of Kelch-like ECH-associated protein (Keap)-1 was increased and expression of nuclear and cytosolic nuclear erythroid 2-related factor 2 (Nrf2) was decreased with TH+IPC vs. NI., Conclusion: TH was the most effective method of protection against early I/R injury. Isolated IPC entailed triggering of second-line antioxidant defense enzymes. Combined TH+IPC seemed to confer no additional advantage over isolated TH in relation to the inflammatory process, but had the advantage of completely avoid second-line antioxidant defense enzymes.

Background: Hepatitis C is a liver disease that causes significant changes in metabolism, and also has an impact on nutritional status., Objective: To evaluate the nutritional status and cardiovascular risk in patients with chronic hepatitis C., Methods: This cross-sectional study investigated 58 patients with chronic hepatitis C, non-cirrhotic and were not under active pharmacological treatment. Patients with significant alcohol consumption (greater than 10 g ethanol/day) were excluded. Patients underwent nutritional assessment through anthropometric measurements and functional assessment using hand grip strength by dynamometry. The physical activity was assessed using the International Physical Activity Questionnaire. Patients also underwent clinical and laboratory evaluation. Cardiovascular risk was calculated by the Framingham score., Results: The mean age of patients was 51.6±9.7 years, 55.2% were female, and 79.3% had genotype 1. The most prevalent degree of fibrosis was F1 (37.9%) followed by F2 (27.6%) and F3 (1.7%). The prevalence of overweight/obesity considering the body mass index was 70.7%. However, 57.7% of men and 68.8% of women were considered malnourished according to hand grip strength. These patients also had waist circumference (93.5±10.7 cm) and neck circumference (37.0±3.6 cm) high. Almost 60% of patients were considered sedentary or irregularly active. In relation to cardiovascular risk, 50% of patients had high risk of suffering a cardiovascular event within 10 years., Conclusion: Although most patients with hepatitis C presented overweight, associated with high cardiovascular risk, they also have reduced functional capacity, indicative of protein-caloric commitment. Therefore, body mass index can not be considered the only method of assessment for nutritional diagnosis of patients with liver disease. Adopting methods such as hand grip strength can be important for a better understanding of nutritional status of these patients.

Background: The hepatitis C virus is one of the main causes of liver disease worldwide and may develop nutritional deficiencies., Objective: The objective of this study was to assess and compare different nutritional status methods of adult patients with chronic hepatitis C virus, and to describe inadequacies in dietary intake., Methods: A cross-sectional study was conducted with adult outpatients with hepatitis C virus at a Brazilian hospital. Nutritional assessment included the 24-hour dietary recall, anthropometry (body weight, height, body mass index, triceps skinfold, mid-upper arm circumference, mid-arm muscle circumference, mid-upper arm muscle area, adductor policis muscle), Subjective Global Assessment, Royal Free Hospital Global Assessment and handgrip strength., Results: A total of 94 outpatients (ages 30 to 76 years), was included, 46 were men. The prevalence of malnutrition as measured by the different methods was 6.4% (body mass index); 60.6% (handgrip strength), and 53.2% (Royal Free Hospital Global Assessment). There was correlation between mid-upper arm circumference and mid-arm muscle circumference (r=0.821), mid-upper arm circumference and triceps skinfold (r=0.575) and mid-upper arm circumference and mid-upper arm muscle area (r=0.781). Energy and protein intakes were below recommended levels in 49 (52.1%) and 44 (46.8%) of patients, respectively. Inadequate calcium, potassium, zinc and vitamin C intakes occurred in 92.6%, 97.9%, 63.8% and 60.6% of patients. There was an association between dietary energy and protein intake with Royal Free Hospital Global Assessment (P<0.001) and a tendency for them to be associated with handgrip strength (P=0.076 and P=0.054)., Conclusion: Malnutrition is frequently in hepatitis C virus patients. They have high prevalence of inadequate energy, protein and micronutrients intake, even in the absence of cirrhosis.

Objectives: 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., Materials and Methods: 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., Results: 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)., Conclusion: 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.

Background and Aims: 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., Materials and Methods: 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., Results: 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., Conclusion: 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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background/aims: 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., Methods: 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., Results: 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., Conclusion: The SNAC solution showed a greater protective effect to preserve rat livers during cold storage, but it was comparable with UW., (Copyright © 2010 Elsevier Inc. All rights reserved.)