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Background Periportal fibrosis is associated with the main complications of schistosomiasis mansoni. The usefulness of hepatic transient elastography (TE) in its evaluation remains to be clarified. Methods We conducted a cross-sectional study of schistosomal patients, where the measurements obtained by FibroScan TE were correlated with the degree of liver fibrosis according to the Niamey sonographic protocol, adopted as the gold standard, and its performance was calculated as the area under the receiver operating characteristics curve (AUROC). Results A total of 117 of 141 adult schistosomiasis patients from endemic areas were selected between May and August 2015. Applying the Niamey protocol, the patients were regrouped into absent fibrosis (A; 34.2%), mild to moderate fibrosis (MM; 27.4%) and intense fibrosis (I; 38.5%). The median of the TE values in the patients of group A was 4.7 kPa, the group MM 9.3 kPa and the group I 10.3 kPa. There was a difference in the TE values between the group A and the groups MM and I (p < 0.05). The TE also presented strong and direct correlation with the clinical form (r ≥ 0.77). The AUROC value to define the presence of fibrosis was 0.92 and for significant fibrosis was 0.79, with cut-offs of 6.1 kPa and 8.9 kPa, respectively. Conclusions In this study, the TE was effective in the diagnosis of schistosomal fibrosis, being able to identify the advanced forms of the disease and thus predict the risk of clinical complications in endemic regions.

Made available in DSpace on 2021-06-25T15:08:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 AbbVie Introduction and objectives: Glecaprevir/pibrentasvir is a highly effective and well tolerated treatment for hepatitis C infection. Brazilian patients were not included in the original development studies for glecaprevir/pibrentasvir. This study aimed to assess safety and efficacy of glecaprevir/pibrentasvir in treatment-naive Brazilian adults without cirrhosis or with compensated cirrhosis. Patients and methods: EXPEDITION-3 was a Phase 3, open-label, multicenter study in treatment-naive Brazilian adults with hepatitis C infection genotype 1-6. Patients without cirrhosis (F2 or F3) or with compensated cirrhosis (F4) received 8 or 12 weeks of glecaprevir/pibrentasvir, respectively. The primary efficacy endpoint was the rate of sustained virologic response at post-treatment Week 12. Secondary endpoints were on-treatment virologic failure and relapse rates. Baseline polymorphisms were assessed in NS3 and NS5A. Adverse events and laboratory abnormalities were monitored. Results: 100 patients were enrolled, 75 received 8 weeks of treatment and 25 received 12 weeks; all patients completed treatment. Overall sustained virologic response at post-treatment Week 12 rate was high (98.0%; 98/100; 95% confidence interval: 93.0-99.4) and remained high regardless of baseline viral or host factors, including demographics, hepatitis C virus RNA levels, polymorphisms in NS3 and/or NS5A, genotype, and relevant comorbidities. 55% of patients reported >= 1 adverse event, the most common being headache (18.0%). Four patients reported serious adverse events; none were considered drug related or led to study drug discontinuation. No hepatic decompensations were observed. Conclusions: Glecaprevir/pibrentasvir was effective and well tolerated in treatment-nave Brazilian patients with hepatitis C infection without cirrhosis and with compensated cirrhosis. (C) 2020 Published by Elsevier Espafia, S.L.U. on behalf of Fundacion Clinica Medica Sur, A.C. This is an open access article under the CC BY-NC-ND license. Hosp Dia, Ave Dr Arnaldo,165, Sao Paulo, Brazil Ramiro Barcelos 2350,CPC Sala,21216, Porto Alegre, RS, Brazil AbbVie Inc, N Chicago, IL USA Inst Infectol Campinas, Rua Dr Quirino,524,Sala 72, Campinas, Brazil Univ Fed Rio Grande do Sul, Sch Med, GI Liver Div, Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil Rua Santa Cruz,81, Sao Paulo, Brazil Rua Diogo Faria,816 Vila Clementino, Sao Paulo, Brazil Univ Sao Paulo, Sch Med, Div Gastroenterol & Hepatol, Ave Eneas Carvalho Aguiar,255 Bloco B 4 Andar, Sao Paulo, Brazil Rua Conego Xavier,276 Amb Infectol, Sao Paulo, Brazil Univ Sao Paulo, Fac Med Ribeirao Preto, Hosp Clin, Unidade Pesquisa Clin, Campus Univ S-N,Bloco G Subsolo 2, Ribeirao Preto, Brazil Univ Fed Maranhao, Clin Hosp Univ, Ctr Pesquisa, Rua Almirante Tamandare,01 Ctr, Sao Luis, Maranhao, Brazil Hosp Ernesto Dornelles, Ave Ipiranga 1801,7 Andar, Porto Alegre, RS, Brazil Ave Mandacaru,1590, Maringa, Parana, Brazil UNESP, Campus Botucatu,Rua Prof Dr Armanda Alves,S-N, Botucatu, SP, Brazil Outclin 5, Marechal Campos Ave 1355, Vitoria, ES, Brazil UNESP, Campus Botucatu,Rua Prof Dr Armanda Alves,S-N, Botucatu, SP, Brazil

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver disease worldwide. Approximately 20% of individuals with NAFLD develop nonalcoholic steatohepatitis (NASH), which is associated with increased risk of cirrhosis, portal hypertension, and hepatocellular carcinoma. Intestinal microflora, including small intestinal bacterial overgrowth (SIBO), appear to play an important role in the pathogenesis of the disease, as demonstrated in several clinical and experimental studies, by altering intestinal permeability and allowing bacterial endotoxins to enter the circulation. OBJECTIVE: To determine the relationship between SIBO and endotoxin serum levels with clinical, laboratory, and histopathological aspects of NAFLD and the relationship between SIBO and endotoxin serum levels before and after antibiotic therapy. METHODS: Adult patients with a histological diagnosis of NAFLD, without cirrhosis were included. A comprehensive biochemistry panel, lactulose breath test (for diagnosis of SIBO), and serum endotoxin measurement (chromogenic LAL assay) were performed. SIBO was treated with metronidazole 250 mg q8h for 10 days and refractory cases were given ciprofloxacin 500 mg q12h for 10 days. RESULTS: Overall, 42 patients with a histopathological diagnosis of NAFLD were examined. The prevalence of SIBO was 26.2%. Comparison of demographic and biochemical parameters between patients with SIBO and those without SIBO revealed no statistically significant differences, except for use of proton pump inhibitors, which was significantly more frequent in patients with positive breath testing. The presence of SIBO was also associated with greater severity of hepatocellular ballooning on liver biopsy. Although the sample, as a whole, have elevated circulating endotoxin levels, we found no significant differences in this parameter between the groups with and without SIBO. Endotoxin values before and after antibiotic treatment did not differ, even on paired analysis, suggesting absence of any relationship between these factors. Serum endotoxin levels were inversely correlated with HDL levels, and directly correlated with triglyceride levels. CONCLUSION: Serum endotoxin levels did not differ between patients with and without SIBO, nor did these levels change after antibacterial therapy, virtually ruling out the possibility that elevated endotoxinemia in non-cirrhotic patients with NAFLD is associated with SIBO. Presence of SIBO was associated with greater severity of ballooning degeneration on liver biopsy, but not with a significantly higher prevalence of NASH. Additional studies are needed to evaluate the reproducibility and importance of this finding in patients with NAFLD and SIBO.

Background: Recent studies suggest that non-alcoholic fatty liver disease (NAFLD) in lean (BMI

Journal of clinical gastroenterology is part of the Juniper publishers which is devoted to publish subject-specific articles focused on the needs of individual research communities across all areas of biology and medicine. Traditionally, elevated serum ferritin is related to the presence of iron accumulation in the body, especially in the liver. However, in chronic hepatitis C several other factors have been alternatively associated with hyperferritinemia, such as liver enzymes, metabolic factors, hepatic steatosis and liver fibrosis. This study aimed to evaluated the exact contribution of these variables to ferritin serum levels in chronic hepatitis.

Non-alcoholic fatty liver disease (NAFLD) currently represents an epidemic worldwide. NAFLD is the most frequently diagnosed chronic liver disease, affecting 20-30% of the general population. Furthermore, its prevalence is predicted to increase exponentially in the next decades, concomitantly with the global epidemic of obesity, type 2 diabetes mellitus (T2DM), and sedentary lifestyle. NAFLD is a clinical syndrome that encompasses a wide spectrum of associated diseases and hepatic complications such as hepatocellular carcinoma (HCC). Moreover, this disease is believed to become the main indication for liver transplantation in the near future. Since NAFLD management represents a growing challenge for primary care physicians, the Asociación Latinoamericana para el Estudio del Hígado (ALEH) has decided to organize this Practice Guidance for the Diagnosis and Treatment of Non-Alcoholic Fatty Liver Disease, written by Latin-American specialists in different clinical areas, and destined to general practitioners, internal medicine specialists, endocrinologists, diabetologists, gastroenterologists, and hepatologists. The main purpose of this document is to improve patient care and awareness of NAFLD. The information provided in this guidance may also be useful in assisting stakeholders in the decision-making process related to NAFLD. Since new evidence is constantly emerging on different aspects of the disease, updates to this guideline will be required in future.

BACKGROUND: Nowadays, pharmacological treatment of non-alcoholic fatty liver disease (NAFLD) is still limited and it is based on the treatment of conditions associated comorbities. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. OBJECTIVE: To evaluate the efficacy of N-acetylcysteine (NAC) in combination with metformin (MTF) and/or ursodeoxycholic acid (UDCA) for treatment of non-alcoholic steatohepatitis (NASH). METHODS: Open-label multicenter randomized trial was conducted for 48 weeks. It included patients with biopsy-proven NASH. The patients were randomized into three groups: NAC (1.2 g) + UDCA (15 mg/kg) + MTF (850-1500 mg/day) (n=26); UDCA (20 mg/kg) + MTF (850-1500 mg/day) (n=13); NAC (1.2g) + MTF (850-1500 mg/day) (n=14) for 48 weeks. Clinical, laboratory and the second liver biopsies were performed after 48 weeks. RESULTS: A total of 53 patients were evaluated; 17 (32.1%) were males; median age ±54 (IQR=15, 21-71) years. In the baseline, no difference was seen between groups according clinical and histological parameters. The groups differed only in cholesterol, LDL and triglycerides. No significant differences in biochemical and histologic parameters were found between these the three groups after 48 weeks of treatment. In the intragroup analysis (intention-to-treat) comparing histological and biochemical features, there were significant improvements in the steatosis degree (P=0.014), ballooning (0.027) and, consequently, in the NAFLD Activity Score (NAS) (P=0.005), and in the ALT levels at the end of the treatment only in the NAC + MTF group. No significant evidence of modification in the liver fibrosis could be observed in any of the groups. CONCLUSION: This multicenter study suggests that the association of NAC + MTF could reduce the liver disease activity in patients with NASH. These data stimulate further controlled studies with this therapy for these patients. RESUMO CONTEXTO: Atualmente, o tratamento farmacológico da doença hepática gordurosa não alcoólica (DHGNA) ainda é limitado e baseia-se no tratamento de condições associadas às comorbidades. O estresse oxidativo e a resistência à insulina são os mecanismos que parecem estar mais envolvidos em sua patogênese. OBJETIVO: Avaliar a eficácia da N-acetilcisteína (NAC) em associação à metformina (MTF) e/ou ácido ursodesoxicólico (UDCA) no tratamento da EHNA. MÉTODOS: Estudo randomizado, multicêntrico e aberto, conduzido por 48 semanas. Incluiu pacientes com esteato-hepatite não alcoólica (EHNA) comprovada por biópsia. Os pacientes foram distribuídos aleatoriamente em três grupos: NAC (1,2 g) + UDCA (15 mg/kg) + MTF (850-1500 mg/dia) (n=26); UDCA (20 mg/kg) + MTF (850-1500 mg/dia) (n=13); NAC (1,2 g) + MTF (850-1500 mg/dia) (n=14) durante 48 semanas. Os dados clínicos, laboratoriais e as segundas biópsias hepáticas foram realizados após 48 semanas. RESULTADOS - Um total de 53 pacientes foram avaliados; 17 (32,1%) eram do sexo masculino; idade mediana de ±54 (IQR=15, 21-71) anos. No baseline, nenhuma diferença foi observada entre os grupos de acordo com parâmetros clínicos e histológicos. Os grupos diferiram apenas em colesterol, LDL e triglicerídeos. Não foram encontradas diferenças significativas nos parâmetros bioquímicos e histológicos entre os três grupos após 48 semanas de tratamento. Contudo, na análise intragrupos (intenção de tratar) comparando características histológicas e bioquímicas, houve melhora significativa no grau de esteatose (P=0,014), balonização (P=0,027) e, consequentemente, no NAFLD Activity Score (NAS) (P=0,005), e nos níveis de ALT no final do tratamento apenas no grupo NAC+MTF. Nenhuma evidência significativa de modificaçãona fibrose hepática pôde ser observada em nenhum dos grupos. CONCLUSÃO: - Este estudo multicêntrico sugere que a associação de NAC+MTF poderia reduzir a atividade da doença hepática em pacientes com EHNA. Esses dados estimulam estudos adicionais controlados com essa terapia para esses pacientes.

Background. Chronic hepatitis C(CHC) staging is important for therapeutic decision-making. Identification of noninvasive markers can provide alternatives to liver biopsy. Aim. To assess the value of APRI and FIB4 for CHC fibrosis staging in a cohort of nonselected outpatients from a referral center in Sao Paulo, Brazil. Material and methods. Medical records of 798 adult outpatients were analyzed retrospectively. For calculations of APRI and FIB4, the original descriptions were considered, and markers were compared with degree of liver injury. Results. Overall, 49.3% of participants were female, and mean age was 56.9 ± 12.5 years. Genotype 1 was predominant (71.7vs. 23.7% genotype 3); 64% had significant fibrosis, 44% had advanced fibrosis, and 28% had cirrhosis. The areas under the receiver operating curve for significant fibrosis, advanced fibrosis, and cirrhosis, respectively, were 0.809, 0.819, and 0.815 for the APRI marker and 0.803, 0.836 and 0.852 for FIB4. Using the recommended cut off values, approximately 30-40% of the patients could not be classified. In the remainder, either APRI or FIB4 alone correctly diagnosed 80-85% of cases. Concomitant or consecutive use of both APRI and FIB4 increased the number of the cases correctly diagnosed only slightly, but also increased the number of patients not classified within the cutoff values. Conclusions. In conclusion, use of the APRI or FIB4 markers for detection of hepatic fibrosis may be a viable alternative at referral centers for treatment of CHC in low- and middleincome countries. Despite relatively good accuracy, a significant number of patients could not be assessed by these methods.

BACKGROUND: Insulin resistance and diabetes mellitus are common extrahepatic manifestations of chronic hepatitis C (HCV). Insulin resistance assessed by HOMA-IR is associated with low rates of sustained virological response, especially in HCV genotype 1 positive patients treated with peginterferon/ribavirin. The effect of insulin resistance on sustained virologic response in HCV genotype 3 positive patients who were treated with peginterferon/ribavirin still remains unclear. OBJECTIVE: To evaluate the impact of insulin resistance on sustained virological response in HCV genotype 3 patients treated with peginterferon/ribavirin. METHODS: A retrospective multicenter study was performed to evaluate the impact of insulin resistance on sustained virological response in non-diabetic HCV genotype 3 positive patients treated with peginterferon and ribavirin. A total of 200 HCV genotype 3 positive patients were enrolled in the study. All patients were non-diabetic. Each patient had a HOMA-IR value measured before the initiation of HCV treatment with peginterferon/ribavirin. The treatment duration was at least 24 weeks. The HOMA-IR cut-off was defined in the study as ≥2.5 due to the coefficient of correlation with sustained virological response of 0.202 (P=0.004). RESULTS: Univariate analysis showed that age, aspartate aminotransferase, platelets, stage of fibrosis and HOMA-IR were predictors of sustained virological response. However multivariate analysis showed advanced fibrosis [OR=2.01 (95%CI: 0.986-4.119) P=0.05] and age [OR=1.06 (95%CI: 1.022-1.110) P=0.002] as negative predictors of sustained virological response. CONCLUSION: In this retrospective multicenter study of non-diabetic HCV genotype 3 positive patients, insulin resistance was not associated with the sustained virological response in patients who were treated with peginterferon/ribavirin.

Introduction: In patients with chronic hepatitis C virus (HCV) infection, 25-hydroxyvitamin D3 [25(OH)D] deficiency has been associated with disease progression and decreased odds of sustained virologic response (SVR) to pegylated interferon and ribavirin combination therapy (PegIFN+RBV). Methods: In this retrospective study, the pretreatment 25(OH)D levels of patients with genotype 1 HCV infection treated with PegIFN + RBV for 48 weeks were measured and correlated with disease stage and periportal necroinflammatory activity (PPA) on liver biopsy, as well as to virologic response at the end of the treatment period. Serum 25(OH)D levels were quantitated by chemiluminescence. Results: Of the 201 patients included, 53% were male and 70% were white, with a mean (SD) age of 46 (±11) years. Subtype 1b was identified in 48% of cases, and 57% of patients had a viral load over 800,000 IU/mL. Overall, 29% of patients had stage 3/4 fibrosis and 40% had grade 3/4 PPA. SVR was achieved in 47% of patients. The mean 25(OH)D concentration was 26.3 (±11.5) ng/mL. Low 25(OH)D levels (

Background & Aims: Hepatitis C (HC) is a major cause of hepatocellular carcinoma (HCC), and a late diagnosis is the main factor for the poor survival of patients. There is an urgent need for identifying sensitive and specific biomarkers for HCC diagnosis. In the present study, plasma lipid patterns of patients with HC-HCC, HC-liver cirrhosis (LC), and chronic HC (CHC) were assessed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).Methods. Plasma samples of 25 patients with HC-HCC, 15 patients with HC-LC, and 25 patients with CHC were evaluated by MALDI-MS using a Q-ToF premier (Synapt) mass spectrometer (Waters, Manchester, UK) equipped with a 200-Hz solid-state laser in the mass range between m/z (mass-to-charge ratio) of 700-1200.Results. A total of 2205 ions were initially obtained and 7 ions (m/z) were highlighted as corresponding to the most important lipids to differentiate HCC patients from LC and CHC patients. The specific lipidomic expression signature generated resulted in an overall predictive accuracy of 93% of HC-HCC and HC-LC, and 100% of HC-HCC and CHC. The 7-peak algorithm distinguished HCC from LC with a sensitivity of 96% and a specificity of 87%, and HCC from CHC with both sensitivity and specificity of 100%.Conclusion. MALDI-MS-specific signature peaks accurately distinguished patients with HC-HCC from those with HC-LC and CHC. The results indicate the potential of MALDI-MS and the selected peaks to improve HCC surveillance in patients with viral C cirrhosis and chronic hepatitis C.

Introduction: A population-based survey conducted in Brazilian capital cities found that only 16% of the population had ever been tested for hepatitis C. These data suggest that much of the Brazilian population with HCV infection remains undiagnosed. The distribution of age ranges at diagnosis and its association with the degree of hepatitis C are still unknown in Brazilian patients. Material and methods: Patients with HCV infection, diagnosed by HCV RNA (Amplicor-HCV, Roche), were included in the study. Patients with HBV or HIV coinfection, autoimmune diseases, or alcohol intake > 20 g/day were excluded. HCV genotyping was performed by sequence analysis, and viral load by quantitative RT-PCR (Amplicor, Roche). The METAVIR classification was used to assess structural liver injury. The Chi-square (χ2) test and student's t-test were used for between-group comparisons. Spearman's rank correlation coefficient were used for analysing the correlation between parameters. Results: A total of 525 charts were reviewed. Of the patients included, 49.5% were male, only 10% of the patients were aged less than 30 years; peak prevalence of HCV infection occurred in the 51-to-60 years age range. Genotype 1 accounted for 65.4% of the cases. Information on HCV subtype was obtained in 227 patients; 105 had subtype 1a and 122 had 1b. According to the degree of structural liver injury, 8.3% had F0, 23.4% F1, 19.8% F2, 11.9% F3, and 36.5% F4. Age at diagnosis of hepatitis correlated significantly with fibrosis (rs = 0.307, p

Background/aims: Controversial results have been found in literature for the association between insulin resistance and sustained virologic response to standard chronic hepatitis C treatment. This study aims to provide a systematic literature review with meta-analysis, in order to evaluate if insulin resistance interferes with sustained virologic response in patients infected by the HCV genotype 1 versus HCV genotypes 2 and 3, undergoing treatment with interferon and ribavirin or pegylated interferon and ribavarin. Methods: Systematic search was performed on main electronic databases until May 2012. Primary outcome was sustained virologic response, defined as undetectable levels of HCV-RNA six months after the end of treatment. Meta-analytic measure was estimated using Dersimonian and Laird's method, using Stata software. Results: Thirteen studies involving 2238 infected patients were included. There was a statistically significant association between insulin resistance and lower sustained virologic response rate, and this difference occurred in HCV genotype G1 (OR: 2.23; 95% CI: 1.59–3.13) and G2/G3 (OR: 4.45; 95% CI: 1.59–12.49). In addition, a difference was seen in the cut-offs used for defining insulin resistance by Homeostasis Model Assessment of Insulin Resistance. To minimize this limitation, sub-analysis that excluded the studies that did not use 2 as a cut-off value was performed and the results still demonstrated association between insulin resistance and sustained virologic response, for both genotypic groups. Conclusion: This meta-analysis provides evidence that elevated Homeostasis Model Assessment of Insulin Resistance is associated with a lower sustained virologic response rate in patients with hepatitis C treated with interferon and ribavirin or pegylated interferon and ribavarin, regardless of their genotype. Keywords: Hepatitis C, Insulin resistance, Genotype, Sustained virologic response

OBJECTIVE: The majority of cases of hepatocellular carcinoma have been reported in individuals with cirrhosis due to chronic viral hepatitis and alcoholism, but recently, the prevalence has become increasingly related to nonalcoholic steatohepatitis around the world. The study aimed to evaluate the clinical and histophatological characteristics of hepatocellular carcinoma in Brazilians' patients with nonalcoholic steatohepatitis at the present time. METHODS: Members of the Brazilian Society of Hepatology were invited to complete a survey regarding patients with hepatocellular carcinoma related to nonalcoholic steatohepatitis. Patients with a history of alcohol intake (>;20 g/day) and other liver diseases were excluded. Hepatocellular carcinoma diagnosis was performed by liver biopsy or imaging methods according to the American Association for the Study of Liver Diseases’ 2011 guidelines. RESULTS: The survey included 110 patients with a diagnosis of hepatocellular carcinoma and nonalcoholic fatty liver disease from nine hepatology units in six Brazilian states (Bahia, Minas Gerais, Rio de Janeiro, São Paulo, Paraná and Rio Grande do Sul). The mean age was 67±11 years old, and 65.5% were male. Obesity was observed in 52.7% of the cases; diabetes, in 73.6%; dyslipidemia, in 41.0%; arterial hypertension, in 60%; and metabolic syndrome, in 57.2%. Steatohepatitis without fibrosis was observed in 3.8% of cases; steatohepatitis with fibrosis (grades 1-3), in 27%; and cirrhosis, in 61.5%. Histological diagnosis of hepatocellular carcinoma was performed in 47.2% of the patients, with hepatocellular carcinoma without cirrhosis accounting for 7.7%. In total, 58 patients with cirrhosis had their diagnosis by ultrasound confirmed by computed tomography or magnetic resonance imaging. Of these, 55% had 1 nodule; 17%, 2 nodules; and 28%, ≥3 nodules. CONCLUSIONS: Nonalcoholic steatohepatitis is a relevant risk factor associated with hepatocellular carcinoma in patients with and without cirrhosis in Brazil. In this survey, hepatocellular carcinoma was observed in elevated numbers of patients with steatohepatitis without cirrhosis.

Background. The epidemiology and clinical characteristics of nonalcoholic fatty liver disease (NAFLD) in South America are not well known. Brazil is a largest country in this part of the world and the present study aimed to contribute with this information. Methods. This descriptive study included patients from medical centers around Brazil, who had diagnosis of NAFLD. They were selected from chart review and also prospectively in Hepatology out-clinics. Patients with history of alcohol intake and others liver diseases were excluded. Histological diagnosis included: steatosis or steatohepatitis (steatosis, ballooning of hepatocytes or fibrosis). The criteria to perform a liver biopsy was ALT or AST > 1.5 x normal levels. Results. A total of 1280 patients from 16 Brazilian centers and all five regions were included. The mean age was 49.68 ± 13.59 years; 53.3% were males and 85% were asymptomatic. Hyperlipidemia was observed in 66.8% cases, obesity in 44.7%, overweight in 44.4%, diabetes in 22.7%, and toxins exposure in 10%. Metabolic syndrome was observed in 41.3% cases. Elevated levels of ALT, AST and GGT were observed in 55.8%, 42.2% and 63.1% cases, respectively. Liver biopsy performed in 437 cases showed: isolate steatosis in 42% cases, steatohepatitis in 58% and 27% of them also presented fibrosis. Cirrhosis was observed in 15.4% and hepatocellular carcinoma in 0.7%. Conclusions. NAFLD in Brazil is more frequent in asymptomatic males; steatohepatitis with fibrosis and cirrhosis were a significant diagnosis. The genetic predisposition and lifestyle should be influenced in the spectrum; however these findings deserve a future investigation.

Background and Aim: Portal hypertensive gastropathy (PHG) is an important cause of bleeding in patients with cirrhosis associated with portal hypertension. Histologically, the condition is characterized by dilation of the mucosal and submucosal vessels of the stomach; however, its mechanisms remain unclear. The aim of the present cross-sectional study was to evaluate the role of portal and systemic hemodynamic features, humoral factors and hepatocellular function in the development and severity of PHG in patients with cirrhosis. Methods: Forty-six patients with cirrhosis of different etiologies underwent endoscopy. Portal hypertension was evaluated by hepatic venous pressure gradient (HVPG). The gastric mucosa was analyzed using two diagnostic methods: endoscopy according to the McCormack criteria and histological by histomorphometric analysis. Results: The prevalence of PHG according to the endoscopic and histomorphometric methods was 93.4% and 76.1%, respectively. There were no statistically significant differences in HVPG measurements between the patients with mild (16.0 ± 5.9 mmHg) and severe PHG (16.9 ± 6.5 mmHg; P = 0.80) or between patients who did not have (15.2 ± 8.0 mmHg) and those who had PHG (16.3 ± 5.7 mmHg). No correlation was found between the presence or severity of PHG and systemic vascular resistance index (P = 0.53 and 0.34, respectively), Child–Pugh classification (P = 0.73 and 0.78, respectively) or glucagon levels (P = 0.59 and 0.62, respectively). Conclusions: The present data show no correlation between the presence or the severity of PHG and portal pressure, Child–Pugh classification or systemic hemodynamics, suggesting that other factors may be involved in the physiopathology of PHG, such as local gastric mucosal factors or other underlying factors.

The prevalence of obesity-related metabolic syndrome has rapidly increased in Brazil, resulting in a high frequency of nonalcoholic fatty liver disease, that didn't receive much attention in the past. However, it has received increased attention since this disease was identified to progress to end-stage liver diseases, such as cirrhosis and hepatocellular carcinoma. Clinical practice guidelines for the diagnosis and treatment of nonalcoholic fatty liver disease have not been established in Brazil. The Brazilian Society of Hepatology held an event with specialists' members from all over Brazil with the purpose of producing guideline for Nonalcoholic Fatty Liver Disease based on a systematic approach that reflects evidence-based medicine and expert opinions. The guideline discussed the following subjects: 1-Concepts and recommendations; 2-Diagnosis; 3-Non-medical treatment; 4-Medical treatment; 5-Pediatrics - Diagnosis; 6-Pediatrics - Non-medical treatment; 7-Pediatrics - Medical treatment; 8-Surgical treatment. RESUMO A prevalência de obesidade relacionada à síndrome metabólica tem crescido no Brasil, que implicou em uma maior frequência de doença hepática gordurosa não alcoólica, não havia recebido muita atenção no passado. Contudo, essa atenção tem merecido interesse cada vez maior desde que se observou o elevado potencial de progressão para formas mais graves dessa doença como cirrose e carcinoma hepatocelular. No Brasil ainda não havia sido proposta nenhuma diretriz para orientar o diagnóstico e tratamento da doença hepática gordurosa não alcoólica. A Sociedade Brasileira de Hepatologia realizou então um evento que reuniu especialistas de todo o Brasil com o objetivo de propor uma diretriz para a doença hepática gordurosa não alcoólica baseada em evidências científicas e opiniões de especialistas nesse tema. A diretriz final é composta dos seguintes temas: 1-Conceitos e recomendações; 2-Diagnóstico; 3-Tratamento não medicamentoso; 4-Tratamento medicamentoso; 5-Diagnóstico em Pediatria; 6-Tratamento não medicamentoso em Pediatria; 7-Tratamento medicamentoso em Pediatria; 8-Tratamento cirúrgico.

OBJETIVO: Revisar a importância da resistência insulínica no desenvolvimento da hepatite C crônica e sua interferência na resposta ao tratamento antiviral de pacientes infectados pelo vírus da hepatite C. FONTE DE DADOS: Revisão bibliográfica de trabalhos publicados pelo MEDLINE e dados dos próprios autores. SÍNTESE DE DADOS: Nos últimos anos, grande número de publicações tem demonstrado importante associação entre resistência insulínica e hepatite C crônica. Aumento na prevalência de diabetes mellitus tipo 2, desenvolvimento de esteatose hepática (principalmente nos pacientes com infecção pelo genótipo não-3), progressão mais rápida da doença e redução na taxa de resposta virológica sustentada ao tratamento com interferon peguilado e ribavirina, têm sido todos associados à presença de resistência insulínica nos pacientes infectados pelo vírus da hepatite C. A produção aumentada de fator de necrose tumoral pelo core do vírus da hepatite C é o principal mecanismo responsável pelo aparecimento da resistência insulínica. O fator de necrose tumoral afetaria a fosforilação do substrato do receptor de insulina diminuindo a captação de glicose e acarretando hiperinsulinemia compensatória. Aumento da siderose hepática e alterações dos níveis circulantes das adipocitocinas podem ter efeito adicional sobre a sensibilidade à insulina na hepatite C crônica. CONCLUSÕES: O diagnóstico e o tratamento da resistência insulínica nesses pacientes podem não só evitar o aparecimento das complicações, mas também prevenir a progressão da doença e, possivelmente, aumentar a taxa de resposta virológica sustentada ao tratamento com interferon peguilado e ribavirina. OBJECTIVE: To revise the importance of insulin resistance in the development of chronic hepatitis C and its interference in the response to the antiviral treatment of these patients. DATA SOURCE: Bibliographic revision of published papers in the MEDLINE and the authors’ data. DATA SYNTHESIS: In the last years several published papers have demonstrated an important relationship between insulin resistance and chronic hepatitis C. Increased prevalence of type 2 diabetes mellitus, the development of hepatic steatosis (specially in non-3 genotype), a more rapid progression of hepatic disease and reduction in the sustained virological response to treatment with pegylated interferon plus ribavirin have been associated with insulin resistance in patients infected with HCV. The mechanism implied in the insulin resistance is the enhanced production of tumor necrosis factor by the HCV core. Tumor necrosis factor affects insulin receptor substrate phosphorylation, resulting in decreased glucose uptake and compensatory hyperinsulinemia. Increased liver iron accumulation and modification in the levels of adipocytokinemia can have an additional effect on insulin sensitivity in chronic C hepatitis. CONCLUSIONS: Diagnosing and treating insulin resistance in patients with chronic hepatitis C could not only avoid complications but also prevent disease progression and increased the sustained virological rate to treatment with pegylated interferon plus ribavarin.

Survival rates of critically ill patients with liver disease has sharply increased in recent years due to several improvements in the management of decompensated cirrhosis and acute liver failure. This is ascribed to the incorporation of evidence-based strategies from clinical trials aiming to reduce mortality. In order to discuss the cutting-edge evidence regarding critical care of patients with liver disease, a joint single topic conference was recently sponsored by the Brazilian Society of Hepatology in cooperation with the Brazilian Society of Intensive Care Medicine and the Brazilian Association for Organ Transplantation. This paper summarizes the proceedings of the aforementioned meeting and it is intended to guide intensive care physicians, gastroenterologists and hepatologists in the care management of patients with liver disease. RESUMO A sobrevida de pacientes cirróticos críticos aumentou significantemente nos últimos anos devido a inúmeros avanços obtidos no manejo do paciente com cirrose descompensada e com insuficiência hepática aguda grave, particularmente após a incorporação na prática clínica de uma série de estratégias baseadas em evidencias com impacto reconhecido na redução de mortalidade. Com o intuito de discutir as principais evidencias disponíveis na literatura médica sobre o assunto, a Sociedade Brasileira de Hepatologia, em conjunto com a Associação de Medicina Intensiva Brasileira e a Associação Brasileira de Transplantes de Órgãos promoveu uma reunião monotemática sobre o manejo do paciente hepatopata crítico, que ocorreu em 21 de maio de 2014 na cidade do Rio de Janeiro. O relatório da reunião foi resumido no presente manuscrito com o objetivo de nortear a prática clínica de intensivistas, gastroenterologistas e hepatologistas no manejo do paciente hepatopata em ambiente de terapia intensiva.

Made available in DSpace on 2018-11-12T17:25:39Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-12-01. Added 1 bitstream(s) on 2018-11-12T17:33:58Z : No. of bitstreams: 1 S0004-28032015000500002.pdf: 416077 bytes, checksum: 27d24d42c1568cacab4536c79600547d (MD5) RESUMO O carcinoma hepatocelular é uma neoplasia de importância global e associada a altos índices de mortalidade. Recentes avanços no diagnóstico e tratamento da doença tornaram necessárias que se atualizassem as recomendações sobre o manejo da doença. Para definir as recomendações sobre o diagnóstico e tratamento do carcinoma hepatocelular, a Sociedade Brasileira de Hepatologia organizou uma reunião monotemática em João Pessoa (PB). Todos expositores foram solicitados a fazer uma revisão sistemática da literatura e apresentar os temas relacionados a fatores de risco para o desenvolvimento de carcinoma hepatocelular, métodos para rastreamento, diagnóstico radiológico e sistemas de estadiamento da doença, tratamentos curativos e paliativos e carcinoma hepatocelular em fígado não cirrótico. Após o encontro, todos os expositores se reuniram para discussão dos tópico e elaboração dessas recomendações. O texto resultante foi ainda submetido a avaliação e aprovação por todos membros da Sociedade através de sua homepage. O documento atual é a versão final que contêm as recomendações da Sociedade Brasileira de Hepatologia. ABSTRACT Hepatocellular carcinoma is a malignancy of global importance and is associated with a high rate of mortality. Recent advances in the diagnosis and treatment of this disease make it imperative to update the recommendations on the management of the disease. In order to draw evidence-based recommendations concering the diagnosis and management of hepatocellular carcinoma, the Brazilian Society of Hepatology has sponsored a single-topic meeting in João Pessoa (PB). All the invited pannelists were asked to make a systematic review of the literature and to present topics related to the risk factors for its development, methods of screening, radiological diagnosis, staging systems, curative and palliative treatments and hepatocellular carcinoma in noncirrhotic liver. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript containing the recommendations of the Brazilian Society of Hepatology. Universidade de São Paulo Faculdade de Medicina Universidade Federal de Ciências da Saúde de Porto Alegre Universidade Federal de Sergipe Hospital Português de Beneficiência Universidade Federal do Mato Grosso Universidade Federal da Bahia Universidade Federal do Rio de Janeiro Universidade Federal de São Paulo Faculdade de Medicina Universidade Federal do Ceará Universidade Federal do Espírito Santo Faculdade de Medicina Universidade Estadual de São Paulo Hospital Santa Catarina Universidade Federal da Paraíba Hospital Português

In order to draw evidence-based recommendations concerning the management of autoimmune diseases of the liver, the Brazilian Society of Hepatology has sponsored a single-topic meeting in October 18th, 2014 at São Paulo. An organizing committee comprised of seven investigators was previously elected by the Governing Board to organize the scientific agenda as well as to select twenty panelists to make a systematic review of the literature and to present topics related to the diagnosis and treatment of autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis and their overlap syndromes. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript organized in topics, followed by the recommendations of the Brazilian Society of Hepatology. RESUMO Para definir as recomendações baseadas em evidências científicas sobre o diagnóstico e tratamento das doenças autoimnus do fígado, a Sociedade Brasileira de Hepatologia organizou em Outubro de 2014, encontro monotemático em São Paulo. Um Comitê organizador de sete investigadores foi selecionado pela Diretoria da Sociedade para organizar a agenda científica, assim como para selecionar vinte debatedores para fazer uma revisão sistemática e apresentar tópicos relacionados à hepatite autoimune, colangite esclerosante primária, cirrose biliar primária e suas síndromes de superposição (overlap). O texto inicial do submetidoo a apreciação e aprovação da Sociedade Brasileira de Hepatologia através de consulta a todos associados através da home page da Sociedade, O trabalho apresentado representa a versão final do trabalho original, devidamente revisado e organizado em tópicos, segundo as recomendações da Sociedade Brasileira de Hepatologia.

Aim: Several noninvasive markers are being used to assess the structural liver damage in patients with chronic hepatitis C (CHC). We evaluated the capacity of serum hyaluronic acid (HA), aspartate aminotransferase (AST)/ALT ratio, the AST to platelet ratio index (APRI) and γ-glutamyltransferase (GGT) levels to predict the intensity of hepatic fibrosis in patients with CHC. Patients and methods: In a total of 206 hepatitis C virus RNA-positive biopsied patients, AST, ALT, GGT levels, platelet count and serum HA concentration were determined. The APRI was calculated as the ratio of AST to platelets. Results: HA levels were best correlated with disease stage (r=−0.694; P

RACIONAL: O teste respiratório da metacetina marcada com carbono 13 (13C-metacetina) é método não-invasivo que permite examinar a função hepática microssomal, permitindo avaliação quantitativa da massa hepática funcional. OBJETIVO: Avaliar a utilidade clinica do teste respiratório da 13C-metacetina na avaliação de pacientes com doença crônica do fígado pelo vírus da hepatite C. CASUÍSTICA E MÉTODOS: Setenta e oito pacientes com hepatite crônica C e 13 indivíduos saudáveis pareados por sexo e idade foram estudados. Pacientes infectados cronicamente pelo vírus C foram classificados como portadores de hepatite crônica (n = 51) ou cirrose hepática (n = 27, sendo 7 deles classificados como descompensados pela presença de ascite, icterícia e/ou encefalopatia). Pacientes co-infectados HbsAg/HIV, em uso crônico de álcool, com outras doenças crônicas ou em uso de medicamentos que pudessem interferir com a atividade do citocromo P450, foram excluídos. O estádio e a atividade da doença nos fragmentos de biopsia foram determinados de acordo com os critérios da Sociedade Brasileira de Hepatologia. O teste respiratório da 13C-metacetina foi realizado com 75 mg de 13C-metacetina e a concentração de 13CO2 no ar expirado foi medido através de espectrometria infravermelha não dispersiva. Foram calculados o "delta over baseline" e o percentual de recuperação cumulativo do 13CO2 aos 40 (teste respiratório da 13C-metacetina 40 min) e aos 120 minutos (teste respiratório da 13C-metacetina 120 min). RESULTADOS: Os parâmetros do teste respiratório da 13C-metacetina se correlacionaram com avaliação estrutural histológica, mas não com a atividade necroinflamatória no tecido hepático, sendo que a melhor correlação foi obtida entre o grau de estádio e o teste respiratório da 13C-metacetina 120 min. Os valores médios do teste respiratório da 13C-metacetina 120 min foram significantemente mais reduzidos nos grupos cirróticos (19,2 ± 7,1% para cirróticos compensados e 14,7 ± 4,0% para os cirróticos descompensados) que nos grupos controle (29,9 ± 4,5%) e com hepatite crônica (27,8 ± 6,1%). A melhor acurácia no diagnóstico de cirrose entre os portadores de hepatite crônica C foi encontrada para o teste respiratório da 13C-metacetina 120 min com 81% de sensibilidade e 77% de especificidade. CONCLUSÃO: O teste respiratório da 13C-metacetina se correlaciona com alterações estruturais encontradas na hepatite crônica pelo vírus C e o percentual de recuperação de 13CO2 aos 120 minutos é um sensível parâmetro para identificar a presença de cirrose nesses pacientes. BACKGROUND: The 13C-methacetin breath test is a non-invasive method to evaluate hepatic microssomal function that allows a quantitative assessment of the functional hepatic mass. AIM: To evaluate the clinical usefulness of the 13C-methacetin breath test in patients with hepatitis C chronic liver disease. PATIENTS AND METHODS: Seventy eight patients with chronic hepatitis C and 13 matched healthy controls were studied. HCV patients were classified as having chronic hepatitis (n = 51), cirrhosis (n = 27), being seven with decompensated disease (presence of ascite, jaundice and/or encephalopathy). HbsAg/HIV co-infected patients, chronic alcohol drinker, having other chronic diseases and those using drugs that could interfere with hepatic cytochrome P450, were excluded. The disease stage and activity in biopsy fragments were determined according the Brazilian Society of Hepatology criteria. Breath test was performed with 75 mg of 13C-methacetin, and the 13CO2 in the expired air was measured through a nondispersive infra red spectrometry. The delta over baseline, and the cumulative recovery of 13CO2 at 40 (13C-methacetin breath test 40 min) and 120 minutes (13C-methacetin breath test 120 min) were calculated. RESULTS: 13C-methacetin breath test parameters correlate only with hepatic staging but not with necroinflammatory (activity) parameters, being the best correlation found between hepatic staging and the 13C-methacetin breath test 120 minutes. The mean values for 13C-methacetin breath test 120 min was significantly reduced in the cirrhotic groups (19.2 ± 7.1% for compensated and 14.7 ± 4.0% for decompensated cirrhotics) than in control (29.9 ± 4.5%) and chronic hepatitis (27.8 ± 6.1%) groups. The best diagnostic accuracy for the diagnosis of cirrhosis among HCV patients was found for 13C-methacetin breath test 120 min with 81% of sensibility and 77% of specificity. CONCLUSION: 13C-methacetin breath test is correlated with structural changes in HCV-related chronic hepatic diseases and the cumulative recovery at 120 minutes is a sensitive parameter to identify the presence of hepatic cirrhosis in these patients.

RACIONAL: Laminina sérica tem sido correlacionada com a hipertensão portal e a capilarização dos sinusóides na doença hepática crônica. Pouco é conhecido sobre sua dinâmica nas doenças hepáticas. OBJETIVO: Estudar os níveis séricos de laminina e correlacioná-los com graus de fibrose hepática e hipertensão portal em ratos tratados com tetracloreto de carbono. MATERIAL E MÉTODO: Quarenta e nove ratos albinos Wistar foram mantidos como controles (n = 16) ou tratados com solução de tetracloreto de carbono a 8% (n = 23). Entre a 6ª e 16ª semana de experimento animais foram sacrificados após cateterização da veia porta e medida da pressão portal. Fragmentos de fígado foram fixados em formol para microscopia óptica. A fibrose hepática foi classificada em perivenular, septal incompleta e completa e cirrose. Concentração de laminina circulante foi determinada pela técnica de ensaio imunoenzimático com anticorpo desenvolvido a partir de laminina isolada de tumor Engelbreth-Holm-Swarm e purificado em coluna de afinidade. RESULTADOS: A pressão portal correlacionou-se com grau de fibrose hepática (r = 0,82; n = 45) e seus níveis nos grupos fibrose septal (10,8 ± 1,2 cm H2O) e cirrose (13,6 + 3,1 cm H2O) foram estatisticamente superiores aos observados no grupo-controle (7,9 + 1,5 cmH2O) e no grupo com fibrose perivenular (9,1 + 0,8 cmH2O). A concentração de laminina no sangue periférico dos cirróticos (40,0 + 18,7 µg/dL) foi significativamente superior aos grupos-controle (13,8 + 12,1 µg/dL), fibrose perivenular (19,1 + 15,5) e fibrose septal (22,2 + 27,0 µg/dL). Laminina circulante correlacionou-se de maneira significativa com o grau de fibrose hepática (r = 0,59; n = 49) e com os níveis de pressão portal (r = 0,29; n = 45). CONCLUSÕES: Na intoxicação crônica experimental pelo tetracloreto de carbono, níveis circulantes de laminina correlacionam-se mais com o grau de fibrose hepática do que com os níveis de hipertensão portal.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third most common cause of cancer death, and accounts for 5.6% of all cancers. Nearly 82% of the approximately 550,000 liver cancer deaths each year occur in Asia. In some regions, cancer-related death from HCC is second only to lung cancer. The incidence and mortality of HCC are increasing in America countries as a result of an ageing cohort infected with chronic hepatitis C, and are expected to continue to rise as a consequence of the obesity epidemic. Clinical care and survival for patients with HCC has advanced considerably during the last two decades, thanks to improvements in patient stratification, an enhanced understanding of the pa-thophysiology of the disease, and because of developments in diagnostic procedures and the introduction of novel therapies and strategies in prevention. Nevertheless, HCC remains the third most common cause of cancer-related deaths worldwide. These LAASL recommendations on treatment of hepatocellular carcinoma are intended to assist physicians and other healthcare providers, as well as patients and other interested individuals, in the clinical decision-making process by describing the optimal management of patients with liver cancer.

The combination of pegylated interferon alfa/ribavirin will likely remain the treatment of choice for HCV genotype 2/3 patients in financially constrained countries for the foreseeable future. Patients with poor on-treatment response may benefit from treatment extension. This study examined the effect of 48 versus 24 weeks of peginterferon alfa-2a/ribavirin on the sustained virological response (SVR) in patients with HCV genotype 2/3 who did not achieve rapid virological response (RVR).N-CORE was a multicentre, randomised, phase III study. HCV genotype 2/3 patients receiving peginterferon alfa-2a/ribavirin without a rapid but with an early virological response were randomised at week 24 to stop treatment (Arm A) or continue to 48 weeks (Arm B). The primary efficacy endpoint was SVR.Two hundred thirty-five patients were enrolled. End of treatment response was similar in both treatment arms. SVR24 rates were not significantly greater in the extended treatment arm compared with the standard 24-week treatment in either the intention-to-treat or the per-protocol populations (61 vs. 52 %, p = 0.1934 and 63 vs. 52 %, p = 0.1461, respectively). Serious adverse events occurred more frequently in patients receiving extended treatment duration (12 %) versus 24-week therapy (4 %).It is unclear whether the extension of peginterferon alfa-2a/ribavirin treatment may benefit HCV genotype 2/3 patients who do not achieve RVR. The study was stopped early because recruitment was slower than anticipated, and this may have limited the statistical impact of these findings.

OBJECTIVES: To present the experience with the first 12 living related liver transplants performed at Hospital Sírio-Libanês in São Paulo. METHODS: The donors were the fathers (6) and the mothers (6) with age ranging from 30 to 48 years. All candidates for donation were submitted to a full informed consent form, clinical and radiological evaluation and had blood withdrawn for autotransfusion. Recipient age ranged from 7 months to 10 years whereas recipient weight varied from 6.3 to 34 kg. Six patients were considered as high risk due to complications of advanced liver disease and were submitted to urgent transplantation. RESULTS: Mean donor hospital stay was 10 days with no mortality. Technical complications were observed in 4 recipients. Seven patients presented at least one episode of bacterial, viral or fungal infection. One or more biopsy proven rejection episodes were disclosed in 7 patients. Overall recipient survival was 67%, being 83% for elective cases and 50% for urgent cases. Long term follow up ranged from 8 to 25 months. Seven out of 8 survivors present excellent quality of life and normal liver function. The other patient is currently under reduced immunosuppression due to Epstein-Barr virus infection.CONCLUSIONS: These results demonstrate the safety and viability of living related liver transplantation which, in face of the current donor scarcity, should be considered as a valid option for the treatment of children with end stage liver disease.

The aim of this study was to validate the Chronic Liver Disease Questionnaire (CLDQ) for use in Brazilian population.A total of 200 patients with chronic liver disease and varying disease severity answered a socio-demographic questionnaire, t CLDQ, and the Medical Outcome Study Short Form 36 (SF-36). Patients returned in 1-15 days to answer CLDQ again. The Cronbach's alpha of the total CLDQ score was 0.95 and fluctuated between 0.69 and 0.83 in its six domains.The intra-class correlation between total CLDQ scores in two evaluations was 0.97 and in all domains was0.93. CLDQ was moderately correlated with the SF-36, 0.63 (total CLDQ vs. vitality, SF-36), 0.62 (CLDQ and mental health, SF-36), 0.62 (preoccupation, CLDQ, vs. General Health, SF-36), 0.59 (fatigue, CLDQ, vs. vitality, SF-36), 0.59 (activity, CLDQ, vs. vitality, SF-36), and 0.59 (fatigue, CLDQ, vs. mental health, SF-36). The highest scores were found in non-cirrhotic group. Child A patients had higher average scores than Child B and C groups in all domains, while patients with MELD15 scored higher than patients with MELD ≥15.CLDQ-BR was validated in Brazilian population and was appropriate for use in patients with liver disease of different etiologies and degrees of severity.

Roche Produtos Quimicos e Farmaceuticos Introduction. A large number of patients with chronic hepatitis C have not been cured with interferon-based therapy. Therefore, we evaluated the efficacy of amantadine combined with the standard of care (pegylated interferon plus ribavirin) in patients who had not responded to or had relapsed after 24 weeks of treatment with conventional interferon plus ribavirin. Material and methods. Patients stratified by previous response (i.e., non-response or relapse) were randomized to 48 weeks of open-label treatment with peginterferon alfa-2a (401(D) 180 pg/week plus ribavirin 1,000/1,200 mg/day plus amantadine 200 mg/day (triple therapy), or the standard of care (peginterferon alfa-2a [40KD] plus ribavirin). Results. The primary outcome was sustained virological response (SVR), defined as undetectable hepatitis C virus RNA in serum (< 50 IU/mL) at end of follow-up (week 72). Among patients with a previous non-response, 12/53 (22.6%; 95% confidence interval [CI] 12.3-36.2%) randomized to triple therapy achieved an SVR compared with 16/52 (30.8%; 95% CI 18.7-45.1%) randomized to the standard of care. Among patients with a previous relapse 22/39 (56.4%; 95% CI 39.6-72.2%) randomized to triple therapy achieved an SVR compared with 23/38 (60.5%; 95% CI 43.4-76.0%) randomized to the standard of care. Undetectable HCV RNA (< 50 IU/mL) at week 12 had a high positive predictive value for SVR. A substantial proportion of non-responders and relapsers to conventional interferon plus ribavirin achieve an SVR when re-treated with peginterferon alfa-2a (40KD) plus ribavirin. Conclusion. Amantadine does not enhance SVR rates in previously treated patients with chronic hepatitis C and cannot be recommended in this setting. Univ Sao Paulo, Sch Med, BR-05403000 Sao Paulo, Brazil Inst Infectol Emilio Ribas, Sao Paulo, Brazil Univ Fed Rio Grande do Sul, Porto Alegre, RS, Brazil Fed Univ Hlth Sci Porto Alegre, Porto Alegre, RS, Brazil State Univ Botucatu, Botucatu, SP, Brazil Pontificia Univ Catolica Campinas, Campinas, SP, Brazil Univ Fed Bahia, Salvador, BA, Brazil Indiana Univ, Indiana, PA USA Univ Fed Sao Paulo, Sao Paulo, Brazil Univ Fed Pernambuco, Recife, PE, Brazil Santa Casa de Misericordia de Goiania, Goiania, Go, Brazil Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil Hosp Alemao Oswaldo Cruz, Sao Paulo, Brazil Roche Prod Quim & Farmaceut, Sao Paulo, Brazil Univ Fed Sao Paulo, Sao Paulo, Brazil Web of Science

CONTEXT: Due to its good correlation to glycemic clamp, HOMA-IR has been widely utilized as insulin resistance index in clinical and epidemiological studies involving non-alcoholic fatty liver disease carriers. However, values used for this parameter have shown large variability. OBJECTIVE: To identify the HOMA-IR cut value that best distinguishes non-diabetic non-alcoholic fatty liver disease patients from a control group. METHODS: One hundred sixteen non-alcoholic fatty liver disease patients were studied, diagnosed by clinical, biochemical, and liver image or biopsy criteria, and 88 healthy individuals, without any liver disease and testing for oral glucose tolerance within normality. These groups did not differ in age and gender. All were submitted to oral glucose tolerance test and blood samples were collected for glucose and insulin measurements by immunofluorometric method. HOMA-IR was calculated according to the formula: fasting insulin (µU/L) x fasting glucose (nmol/L)/22.5. RESULTS: NAFLD patients showed higher insulin, glycemia, and HOMA-IR values than control group, even when excluding glucose intolerant and diabetes mellitus patients by their glycemic curves. HOMA-IR 75th percentile for control group was 1.78 and the best area under the curve index was obtained for HOMA-IR values of 2.0 [AUC= 0.840 (0.781-0.899 CI 95%), sensitivity (Se): 85%, specificity (Sp): 83%] while value 2.5 showed best specificity without important loss in sensitivity [AUC=0,831 (0.773-0.888) Se = 72%, Sp = 94%]. CONCLUSION: HOMA-IR values above or equal to 2.0 or 2.5 show enhanced diagnostic value in distinguishing non-alcoholic fatty liver disease carriers from control group individuals. CONTEXTO: Pela sua boa correlação com o "clamp" glicêmico, o HOMA-IR tem sido largamente utilizado como índice de resistência insulínica em estudos clínicos e epidemiológicos em pacientes com doença hepática gordurosa não-alcoólica. Porém os valores utilizados para esse parâmetro têm sido muito variáveis. OBJETIVO: Identificar o valor de corte do HOMA-IR que melhor diferencie pacientes com doença hepática gordurosa não-alcoólica não-diabéticos, de um grupo controle. MÉTODOS: Foram estudados 116 pacientes com doença hepática gordurosa não-alcoólica, diagnosticados por critérios clínicos, bioquímicos e de imagem ou biopsia hepática e 88 indivíduos saudáveis, sem doença hepática e com teste de tolerância oral à glicose dentro da normalidade. Esses grupos não diferiam quanto à idade e gênero. Todos foram submetidos ao teste de tolerância oral à glicose e coletadas amostras de sangue para dosagem de glicemia e de insulina através de método imunofluorimétrico. Foi feito o cálculo do HOMA-IR de acordo com fórmula = insulina de jejum (µU/L) x glicemia de jejum (nmol/L)/22.5. RESULTADOS: Os pacientes com doença hepática gordurosa não-alcoólica apresentaram valores mais elevados de insulina, glicemia e HOMA-IR que o grupo controle, mesmo quando excluídos os pacientes com diagnóstico de intolerância à glicose ou de diabetes mellitus pela curva glicêmica. O percentil 75 para HOMA-IR no grupo controle foi de 1.78 e o melhor índice de área sob a curva foi obtido para os valores de HOMA-IR de 2,0 [ASC = 0,840 (0,781-0,899 IC95%), sensibilidade: 85%, especificidade: 83%] enquanto o valor de 2,5 foi o que apresentou melhor especificidade, sem perda importante de sensibilidade [ASC = 0,831 (0.773-0.888) sensibilidade: 72%, especificidade: 94%] . CONCLUSÃO: Valores de HOMA-IR acima ou iguais a 2.0 ou 2.5 mostram elevado valor diagnóstico na distinção entre os doentes com doença hepática gordurosa não-alcoólica e indivíduos do grupo controle.

Background and Aims: Most studies published focus on the evaluation of the impact of nutritional status on the morbidity and mortality during the immediate postoperative period or on the short-term evolution of liver transplant patients. The aim of the study was to evaluate long-term trends in nutritional status. Methods: Seventy patients consecutively submitted to liver transplantation were studied. Nutritional assessment was performed the day before transplantation and the 45, 90, 180 and 365 days after transplantation, consisting of determination of dietary intake, anthropometric and biochemical analysis. Results: Sixty-nine percent of the patients presented with malnutrition on the day before liver transplantation, decreasing to 44% at end of the first year. The prevalence of protein–calorie malnutrition (PCM) was 63% at 90 days post-transplant. A significant difference of PCM was observed between patients with cirrhosis and non-cirrhotic disease (53.6% × 100%) at 90 days post-transplant. The pre-transplant nutritional diagnosis and 90-day calorie intake were identified as variables independently associated with nutritional status at 90 days post-transplant. The variables independently associated with nutritional status in the 1-year assessment were pre-transplant PCM and 365-day calorie requirements. Conclusion: No influence on nutritional status was observed for peri- or postoperative factors after 3 or 12 months of follow up. As expected, dietary factors, especially adequate calorie intake, were always associated with nutritional status during all periods analyzed.

CONTEXT: Experimental and clinical studies suggest that LOLA may have a favorable influence on hepatic encephalopathy due to the effect on the reduction of ammonia, and improvement of the symptoms and laboratory findings. OBJECTIVES: To evaluate and to critically analyze the efficacy and/or effectiveness results of the use of LOLA when compared to placebo in the treatment of hepatic encephalopathy. DATA SOURCES: LILACS, SciELO, MEDLINE, PubMed database and Cochrane Collaboration Register of Controlled Trials were searched from 1966 to September of 2006. The review has included all the randomized controlled double-blind clinical trials performed in humans in English language. RESULTS: Four studies published between 1993 and 2000 were selected and reviewed. LOLA was showed as being able to reduce hyperammonemia in patients with hepatic encephalopathy, when compared to patients in the placebo group. CONCLUSIONS: Although the trials have shown efficacy of LOLA in reducing hyperammonemia of hepatic encephalopathy, sufficient evidence of a significant beneficial effect of LOLA on patients with hepatic encephalopathy was not found. The studies performed in this area were small, with short follow-up periods and half of them showed low methodological quality. CONTEXTO: Estudos experimentais e clínicos sugerem que a L-ornitina-L-aspartato pode ter uma influência favorável na encefalopatia hepática em virtude do seu efeito na redução da amônia, e melhora dos sintomas e achados laboratoriais. OBJETIVOS: Avaliar e analisar criticamente os estudos de eficácia e/ou efetividade do uso de L-ornitina-L-aspartato quando comparado com placebo no tratamento da encefalopatia hepática. FONTES DE INFORMAÇÃO: Foram pesquisadas as bases de dados LILACS, SciELO, MEDLINE, PubMed e o Registro de Ensaios Controlados da Colaboração Cochrane no período de 1966 até setembro de 2006. A revisão incluiu todos os ensaios clínicos controlados randomizados, duplo-cego, em seres humanos, no idioma inglês. RESULTADOS: Foram selecionados e revisados quatro estudos publicados entre 1993 e 2000, que mostraram que a L-ornitina-L-aspartato foi capaz de reduzir a hiperamonemia em portadores de encefalopatia hepática, quando comparados ao grupo que utilizou placebo. CONCLUSÕES: Embora os estudos tenham demonstrado eficácia da L-ornitina-L-aspartato em reduzir a hiperamonemia da encefalopatia hepática, não foi encontrada evidência suficiente que a L-ornitina-L-aspartato tenha um efeito clínico benéfico significativo em pacientes com encefalopatia hepática. Os ensaios realizados neste campo foram pequenos com períodos curtos de acompanhamento e a metade deles com baixa qualidade metodológica.

INTRODUCTION: The main extra-hepatic manifestation of hepatitis C is mixed cryoglobulinemia (MC). The aim of this study was to evaluate its prevalence among patients with chronic hepatitis C (CHC), to correlate its presence to host and virological variables and to the response to combined therapy with interferon-alpha and ribavirin. CASUISTIC AND METHODS: 202 CHC naive patients (136 with chronic hepatitis and 66 with cirrhosis) were consecutively evaluated for the presence of cryoglobulins. Cryoprecipitates were characterized by immunoelectrophoresis and classified according to the Brouet's criteria. RESULTS: The prevalence of MC was 27% (54/202), and 24% of them (13/54) showed major clinical manifestation of the disease. Even though type III MC was more frequent (78%), symptomatic MC was more common in type II MC. The presence of cirrhosis (RR = 2.073; IC95% = 1.029 - 4.179; p = 0.041), and age of the patients (RR = 1.035; IC95% = 1.008 - 1.062; p = 0.01) were independently associated with the presence of cryoglobulins. No relationship was found with viral load and genotype. 102 patients were treated with interferon alpha and ribavirin. Among these, 31 had MC. Sustained virological response (around 30%) was similar in patients with and without MC (p = 0.971). CONCLUSION: MC represents a prevalent complication in patients with CHC, specially older and cirrhotic patients. Only 24% of these patients show clinical manifestation of the disease, specially those with type II MC. The presence of MC did not affect the response to therapy. INTRODUÇÃO: A crioglobulinemia mista (CM) representa importante complicação extra-hepática da hepatite C. Nesse estudo avaliamos sua prevelência em pacientes com hepatite C crônica (HCC) e relacionamos sua presença com aspectos clínicos e resposta ao tratamento com interferon alfa e ribavirina. CASUÍSTICA E MÉTODOS: 202 pacientes consecutivos com HCC (136 com hepatite crônica e 66 com cirrose) foram avaliados para a presença de CM. Os crioprecipitados foram caracterizados por imunoeletroforese e classificados de acordo com BROUET et al. RESULTADOS: A prevalência de CM nessa população foi de 27% (54/202), e, desses, 24% (13/54) apresentaram manifestações clínicas maiores da doença. Embora MC tipo III tenha sido a forma mais freqüentemente encontrada, a doença sintomática foi mais comum entre os pacientes com MC tipo II. A presença de cirrose (RR = 2,073; IC95% = 1,029 - 4,179; p = 0,041) e a idade do paciente (RR = 1,035; IC95% = 1,008 - 1,062; p = 0,01) estiveram independentemente associadas à presença de CM. Não houve associação entre a presença de CM e genótipo ou carga viral do vírus C. No total, 102 pacientes foram tratados com interferon alfa e ribavirina. Desses, 31 apresentavam CM. A resposta virológica sustentada (em torno de 30%) não diferiu entre pacientes com e sem CM (p = 0,971). CONCLUSÃO: CM é uma freqüente complicação na HCC, especialmente em pacientes com idade avançada e com cirrose hepática. Apenas 24% desses pacientes apresentam manifestações clínicas da doença, sendo mais freqüentes entre portadores de CM tipo II. A presença de crioglobulinemia não afetou a resposta virológica ao tratamento com interferon alfa e ribavirina.

The combined therapy with interferon alfa plus ribavirin (INF+RBV) is considered the most appropriate treatment for patients with chronic hepatitis C virus genotypes 2 and 3 in Brazil. However, wide variations in the rates of sustained viral response (SVR) have been reported among such patients. We evaluated, retrospectively, factors associated with SVR in subjects with chronic hepatitis C virus genotypes 2 and 3 and that received medication from the Health Secretariat of the state of São Paulo. One-hundred-seventy-seven consecutive patients with chronic hepatitis C were treated for 24 or 48 weeks according to the viral genotype. Patients co-infected with associated hepatic diseases or who had problems with alcohol abuse were excluded. The genotype of the HCV-RNA was identified through restriction analysis, the viral load through quantitative PCR (Amplicor, Roche) and the degree of hepatic fibrosis according to the Metavir score. Demographic, virological and histological parameters were submitted to binary logistic regression analysis to identify the variables associated with SVR. The overall rate of SVR was 36.4% for the 177 patients, and genotype 2 or 3 was the main parameter independently associated with SVR. Among the 77 patients with these viral genotypes, only the stage of fibrosis had a significant effect on the SVR (odds ratio (OR) = 3.035; 95% CI (confidence interval) = 1.196-7.699; p=0.019). The rate of SVR among the subjects with fibrosis at an advanced stage (F3-F4) was 38%, compared to 75% for patients with fibrosis at an initial stage (F0-F2). Consequently, other therapeutic options should be considered for patients with genotypes 2 and 3 who have advanced fibrosis.

BACKGROUD: Protein-calorie malnutrition is a frequent finding in patients with chronic liver disease, but investigations of nutritional status have been rarely performed in individuals seen at outpatient clinics AIM: To evaluate the nutritional status of patients with alcoholic and nonalcoholic cirrhosis, attended for the first time at a reference outpatient clinic for liver diseases. PATIENTS AND METHODS: A total of 300 consecutive patients attended at the outpatient clinics of a reference center for liver diseases were investigated. Anthropometric evaluation was performed by the usual parameters: triceps skinfold, arm circumference and arm muscle circumference. Biochemical parameters included creatinine/height index, serum albumin and lymphocytes count. The nutritional diagnosis was based on the PCM score proposed by Mendenhall et al. Food intake was retrospectively evaluated using 24-hour dietary recall data. RESULTS: About 71% of the patients studied were chronic alcohol abusers, whereas in 29% cirrhosis was of nonalcoholic etiology. Independently of the disease etiology 75.3% of the patients showed some degree of protein-calorie malnutrition, which was moderate or severe in 38.3% of them. More advanced protein-calorie malnutrition degrees were associated with lower energy and protein intake. The prevalence of moderate or severe protein-calorie malnutrition was higher in patients classified as Child-Pugh C than in patients classified as Child-Pugh A (21% x 58%, respectively). Regarding sexual differences, fat reserves, evaluated by triceps skinfold, were more depleted in females than in males (48.6% x 26.6%) regardless of the etiology of the cirrhosis, whereas muscle reserves (arm muscle circumference) were more depleted in males (43.4% x 13.4%) regardless of the etiology of cirrhosis. In contrast, cirrhosis of alcoholic etiology was determinant in reducing arm muscle circumference in females (20% x 9.1%) CONCLUSIONS: These data highlight the high prevalence of protein-calorie malnutrition occurring early in the natural history of the disease and accompanying functional hepatic deterioration. In addition, attention should be paid to the different gender patterns of response to protein-calorie malnutrition in these patients. RACIONAL: A desnutrição calórica e protéica é achado freqüente em pacientes com doença hepática. Poucas investigações da desnutrição calórica e protéica têm sido realizadas em pacientes atendidos em ambulatório OBJETIVO: Avaliar o estado nutricional de pacientes com cirrose hepática (alcoolistas e não-alcoolistas), atendidos na primeira consulta em ambulatório de referência para doenças hepáticas. PACIENTES E MÉTODOS: Trezentos pacientes consecutivamente atendidos pela primeira vez em ambulatório de doenças hepáticas foram incluídos neste estudo. Os mesmos foram submetidos a avaliação nutricional que constou de antropometria: dobra cutânea do tríceps, circunferência do braço e circunferência muscular do braço, e bioquímica: índice creatinina/altura, albumina sérica e contagem total de linfócitos. O diagnóstico do estado nutricional foi baseado pelo escore de desnutrição calórica e protéica proposto por Mendenhall e colaboradores e a ingestão alimentar por recordatório de 24 h RESULTADOS: Setenta e um porcento dos pacientes cirróticos estudados foram de causa alcoólica e 29% não-alcoólica. Independentemente da causa, a prevalência de desnutrição calórica e protéica foi de 75,3%, sendo que 38.3% deles já a apresentavam moderada e grave. Os pacientes com desnutrição calórica e protéica moderada e grave apresentavam pior ingestão de proteína e energia. A prevalência de moderada e grave foi mais elevada nos pacientes classificados como Child-Pugh C do que nos pacientes classificados como Child-Pugh A (21% x 58%, respectivamente). Em função das variáveis sexo e causa, as reservas de gordura, avaliadas pela dobra cutânea do tríceps, estiveram mais depletadas em mulheres cirróticas que nos homens cirróticos (48,6% x 26,6%). Já as reservas musculares, avaliadas por circunferência muscular do braço, estiveram mais depletadas em homens cirróticos (43,4% x 13,4%), independentemente da causa da cirrose. Em contraste, mulheres cirróticas alcoólicas apresentaram maior redução de circunferência muscular do braço que nas mulheres não-alcoólicas (20% x 9,1%) CONCLUSÕES: Os pacientes cirróticos já apresentavam elevada prevalência de desnutrição calórica e protéica na primeira consulta em ambulatório, principalmente nos pacientes com piora da função hepática. A variável sexo é outro aspecto que deve ser enfocado pois influenciou aspectos antropométricos (circunferência muscular do braço e dobra cutânea do tríceps) nesses pacientes.

Laminin levels in ascitic fluid have been proposed as a marker for neoplastic ascites. We compared the concentration of laminin in serum and in ascitic fluid from patients with hepatic cirrhosis and peritoneal carcinomatosis and assessed the diagnostic value of serum laminin levels in differentiating neoplastic from benign ascites. Laminin concentrations were determined by ELISA with antibodies against laminin extracted from the human placenta, in patients with ascites due to peritoneal carcinomatosis (N = 20) and hepatic cirrhosis (N = 33). Patients with infected or hemorrhagic ascites were excluded. The receiver operating characteristic curve was used to determine the sensitivity and specificity of serum laminin for the diagnosis of neoplastic ascites. When compared to the group with cirrhosis, the carcinomatosis group presented significantly higher mean laminin levels in serum (3.3 +/- 0.5 vs 2.1 +/- 0.4 microg/ml, mean +/- SD, P0.05) and ascites (2.8 +/- 0.5 vs 1.6 +/- 0.4 microg/ml, P0.05). Although laminin concentration was higher in serum than in ascites, the laminin serum/ascites ratio and serum-ascites gradient did not differ between the studied groups. A significant correlation (r = 0.93, P0.0001) was observed between the serum and ascites laminin values. Serum laminin levels2.25 microg/ml showed 100% sensitivity and 73% specificity for the diagnosis of neoplastic ascites. Serum concentration seems to be the main determinant of laminin levels in ascitic fluid and its values can be used as a diagnostic parameter in the study of neoplastic ascites.

e15155 Background: Werecently described the antiproliferative effects of low levels of electromagnetic fields, amplitude-modulated at disease-specific frequencies (AM EMF) in patients with HCC (Br J Cancer, 2011,105:640) and on HCC cells (Br J Cancer, 2012,106:307). We identified HCC-specific modulation frequencies using a patient based biofeedback approach (J Exp Clin Cancer Res, 2009,28:51). Specific frequencies cause changes in pulse pressure in patients with HCC but not in healthy individuals. The effects of AM EMF in HBsAg+ patients, a pre-malignant condition, are unknown. Methods: 17 healthy individuals and 17 patients (5 HCC and 12 HBsAg+) were exposed to 206 HCC-specific modulation frequencies ranging from 100 Hz to 21 kHz (HCC-frequencies) and 237 random chosen frequencies (non-specific frequencies) within the same frequency range. All participants were exposed to both AM EMF and each frequency was tested separately. Changes in pulse pressure were recorded as previously described (J Exp Clin Cancer Res, 2009, 28:51). Results: HCC-frequencies caused changes in pulse pressure in all HBsAg+ and patients with HCC but no changes were observed in healthy individuals. The median number of frequencies causing changes in pulse pressure in patients with HCC was 175 (range: 97-206) and 7 (range: 3-16) in HBsAg+ patients. The non-specific frequencies did not cause changes in pulse pressure in patients with HCC but it caused changes in pulse pressure in 9 HBsAg+ (75%) with a median number of responding frequencies of 2 (range: 1-6). Non-specific frequencies also caused changes in pulse pressure in 11 healthy individuals (64%) with a median number of responding frequencies of 11 (range: 1-15). The pattern of changes in pulse pressure were significant between the 3 groups (p=0.0001). Conclusions: EMF modulated at specific frequencies cause a significantly different pattern of changes in pulse pressure in the three groups. These findings provide support for the development of EMF as a new diagnostic procedure. Clinical trial information: NCT01641276.

Results Patients 1 and 3 were diagnosed late, by the age of 54 and 43 yrs. respectively. While the second patient was diagnosed earlier at 17th and follows 14 yrs. in treatment. All patients have low body fat on DEXA (Figure 1) and moderate steatosis, but only the Patient 2 has no fibrosis. The patients’ metabolic profile after the treatment is exposed at Table 1. All patients are in use, at least for 2 yrs., of TZD (30 mg/day), MTF (2000mg/day), insulin (2.01 UI/kg±0.36) and atorvastatin (20-40 mg/day ). Only Patients 2 and 3 are in use fibrate because the Patient 1 had CPK elevation with this. Patient 2 fundoscopy showed significant deposition of triglycerides in her retina (Figure 2).

O hipertireoidismo leva o fígado a uma situação de proteção antioxidante limítrofe, que pode aumentar a susceptibilidade do órgão a ações deletérias de xenobióticos ou fenômenos que impliquem em estresse oxidativo. Tal ocorre em ratos Sprague-Dawley tratados simultaneamente com hormônio tireoidiano L-3,3\',5-triiodotironina (T3) e o inseticida lindano (gama-hexaclorociclohexano). Enquanto a dose única de lindano (20 mg/kg peso corpóreo) não alterou a maioria dos parâmetros estudados, a administração de T3 estabeleceu a condição de estresse oxidativo hepático pelo aumento da atividade da NADPH-citocromo c redutase, acompanhado do aumento nos índices de lipoperoxidação e da produção microssomal de ânion superóxido (O2-) e da diminuição da atividade de defesas antioxidantes enzimáticas (superóxido dismutase e catalase) e não-enzimáticas (diminuição dos níveis hepáticos de alfa-tocoferol, beta-caroteno e licopeno). A administração de lindano teve seu efeito potenciado pelo hipertireoidismo, como indicado pelo aumento das razões O2-/SOD e SRAT/GSHT e pela diminuição dos níveis de alfa-tocoferol hepático, ambos efeitos maiores do que a soma dos obtidos nos tratamentos isolados. Devido à importância da atividade dos macrófagos residentes no fígado, observada em vários modelos de dano hepático, a função das células de Kupffer (CK) foi estudada neste modelo. Ao contrário do observado em experimentos no fígado íntegro, a luminescência das CK isoladas sofreu decréscimo nos animais tratados com T3 e lindano separadamente, apresentando uma tendência ao aumento no tratamento conjunto. Todos os tratamentos diminuíram a atividade fungicida das CK. É possível que os tratamentos utilizados estejam prejudicando a ação das CK, sendo restaurada na presença dos dois tratamentos. Por outro lado, a importância das CK no aumento do efeito do lindano no hipertireoidismo experimental foi evidenciada pela supressão dos efeitos acima mencionados após a administração do inativador de CK, o GdCl3. Estudos morfológicos corroboram este dado, mostrando uma supressão de sinais inflamatórios e necróticos nos animais hipertiroídeos tratados com GdCl3. Hyperthyroidism elicits a borderline antioxidant protection state in the liver, which may increase its susceptibility to deleterious effects of xenobiotics or situations that cause oxidative stress. This happens to Sprague-Dawley rats treated concurrently with thyroid hormone L-3,3\',5-triiodothyronine (T3) and the pesticide lindane (gama-hexachlorocyclohexane). While a single dose of 20 mg/kg body weight of lindane did not alter most of the assessed parameters, T3 administration established a hepatic oxidative stress condition by means of an increase in NADPH-cytochrome c reductase activity, with a concomitant increase in lipoperoxidation (increase of thiobarbituric acid reactants) and microsomal generation of superoxide anion (O2-) and lower enzymatic (decreased activities of superoxide dismutase (SOD) and catalase) and non-enzymatic antioxidant defenses (decreased hepatic levels of alpha-tocopherol, beta-carotene, and lycopene). Lindane administration had potentiated effects on hyperthyroid animals, as indicated by the increased O2-/SOD ratio and further lowering of alpha-tocopherol levels in the liver; both effects greater than the sum of the ones observed after isolated treatments. As liver resident macrophages have been shown to play an important role in several hepatic damage models, Kupffer cell (KC) function was also studied in this model. Contrary to what was observed in experiments in the whole liver, Kupffer cell (KC) luminescence was diminished in separately T3 and lindane treated rats, revealing a tendency to increase after joint treatment. All treatments decreased KC fungicidal activity. It is possible that the separate treatments impair KC function, which is restored after the joint treatment. KC role in the potentiation of lindane-induced oxidative stress was evidenced by the suppression of this effect after KC inactivator, gadolinium chloride, administration. Morphological aspects of liver corroborate these data, showing a suppression of inflammatory and necrotic signals, present in hyperthyroid animals treated with lindane.