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ABSTRACT Background: Spontaneous regression (SR) is defined as the partial or complete disappearance of a tumor, in the absence of a specific treatment. Evidence of the SR in hepatocellular carcinoma (HCC) is rare. Objective: The authors aimed to review all the cases of SR of HCC in two reference centers of Southern Brazil, highlighting the main characteristics. Methods: Data of all patients with HCC were retrospectively reviewed looking for the occurrence of SR in patients from two tertiary centers in Southern Brazil, in the last five years. The diagnosis of cirrhosis was established according to clinical, laboratory and imaging data, as well as upper endoscopy or histopathological examination when necessary. The diagnosis of HCC was based on typical findings according to radiologic criteria (LIRADS) or histopathological examination. Spontaneous regression was defined as a partial or complete involution of a HCC in the absence of a specific therapy. Results: From all cases of HCC in the last 5 years (n=433), there were five cases of SR. Three (60%) were men, the mean age was 62.6 (50.0-76.0) years, and the etiology was HCV in 3 (60%). Complete regression was observed in three patients (60%), one patient (20%) presented partial regression, and one (20%) relapesed and died. The time of follow-up varied between 12 and 21 months. In this presentation, it was highlighted one case of SR observed after COVID-19 infection in a patient with cirrhosis. The possible mechanisms involved in this situation were reviewed, emphasizing the most common like hypoxia and immunological. There were also one patient submitted to a surgical procedure as a possible fator involved and three patients without obvious risk factors. Conclusion: This phenomenon will possibly contribute to a better understanding of the pathophysiological mechanisms of HCC.

ABSTRACT This is a narrative review that aims to discuss the importance of elastographic methods in the evaluation of clinically significant portal hypertension (CSPH) in cirrhotic patients, where the authors propose an algorithm for evaluating these patients. In compensated advanced chronic liver disease, the goal is to prevent the development of CSPH and, in those already with CSPH, prevent the appearance of gastroesophageal varices (GEV) and other complications of portal hypertension. In compensated cirrhosis, the prevalence of GEV is 30-40%, of which 10-20% are at risk of bleeding. Therefore, using non-invasive methods would exempt the patient from the need of an endoscopy. Hepatic Elastography is a non-invasive, safe, reproducible method, available through many techniques: Vibration-Controlled Transient Elastography (VCTE), Shear Wave Elastography (SWE) and Magnetic Resonance Elastography (MRE). The Baveno VII presented the “rule of 5” for VCTE: liver stiffness measurement (LSM) ≤15 kPa and platelets >150.000/mm3 exclude CSPH, while an LSM ≥25 kPa is highly suggestive of CSPH. Also, the “rule of 4” for SWE has been proposed: patients with ≥17 kPa could be considered as having CSPH. At last, spleen stiffness measurement (SSM) has been proposed as a more specific technique to predict the presence of CSPH. In conclusion, elastography has gained prestige in the non-invasive evaluation of patients with advanced chronic liver disease by allowing prophylactic measures to be taken when suggesting the presence of CSPH.

ABSTRACT BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in the world, and its prevalence is increasing alongside obesity. In United States, NAFLD is already the second leading cause of liver transplantation. The spectrum of the disease ranges from simple steatosis, which has a benign course, to steatohepatitis, which may progress to cirrhosis and its complications. The rising of noninvasive methods for diagnosing and staging non-alcoholic steatohepatitis (NASH) and fibrosis decreases the need of liver biopsy, as well as the costs and the occurrence of complications related to it. OBJECTIVE: To analyze the performance of the triglyceride-glucose index to evaluate steatosis, NASH and liver fibrosis in obese patients with NAFLD. METHODS: This is a retrospective cross-sectional study. Every medical record of patients who were candidates for bariatric surgery at a leading hospital in Southern Brazil were analyzed. The triglyceride-glucose index (TyG Index), a method composed only of two simple laboratory tests (serum triglycerides and fasting glucose levels), was performed prior to surgery. The TyG Index performance regarding the anatomopathological findings was evaluated, and the AUROC curve was calculated to evaluate the best cut-off point for diagnosing steatosis, non-alcoholic steatohepatitis and liver fibrosis grade. Also, the NAFLD fibrosis Score (NFS) was evaluated. RESULTS: A total of 423 patients were evaluated. The TyG Index with a cut-off point of 8.76 excluded significant simple steatosis (grade 2-3) in obese patients, with 67.6% sensitivity, 65.1% specificity, 46.3% positive predictive value (PPV), 81.8% negative predictive value (NPV), 65.8% accuracy and 0.66 AUROC (P=0.005). In the evaluation of NASH, the TyG Index with a cut-off point of 8.82 excluded significant NASH (grade 2-3) with 57.3% sensitivity, 58.6% specificity, 33.7% PPV, 78.8% NPV, 58.2% accuracy and 0.58 AUROC (P=0.022). When evaluating liver fibrosis, the TyG Index with a cut-off point of 8.91 showed a sensitivity of 61.8%, a specificity of 62.5%, a PPV of 13.8 and a NPV of 94.4% for exclusion of advanced fibrosis (F3-4), with a 62.4% accuracy and 0.69 AUROC (P

ABSTRACT BACKGROUND: Hepatocellular carcinoma (HCC) is the most frequent primary cancer of the liver and cirrhosis is considered a pre-malignant disease. In this context, the evolutionary sequence from low grade dysplastic nodule and high grade dysplastic nodule (HGDN) to early HCC and advanced HCC has been studied. The differential diagnosis between HGDN and early HCC is still a challenge, especially in needle biopsies OBJECTIVE: To evaluate an immunohistochemistry panel to differentiate dysplastic nodules and HCC. METHODS: Patients with cirrhosis who underwent surgical resection or liver transplantation were included. The sensitivity, specificity and accuracy for the diagnosis of neoplasia were analyzed by evaluating five markers: heat shock protein 70, glypican 3, glutamine synthetase, clathrin heavy chain and beta-catenin. P≤0.05 was considered statistically significant. RESULTS: One hundred and fifty-six nodules were included; of these, 57 were HCC, 14 HGDN, 18 low grade dysplastic nodules and 67 regenerative macronodules. Sensitivity of HCC diagnosis was 64.9% for glypican 3 and 77.2% for glutamine syntetase, while specificity was 96.0% and 96.0% respectively. When the panel of four markers was considered (excluding beta catenin), the specificity ranged from 87.9% for one positive marker to 100% for at least three markers. The best accuracy for HCC diagnosis was obtained with at least two positive markers, which was associated with a sensitivity of 82.5% and specificity of 99%. CONCLUSION: Differential diagnosis of dysplastic nodules and HCC by morphological criteria can be challenging. Immunomarkers are useful and should be used for the differential diagnosis between HCC and HGDN.

ABSTRACT Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2015 its first recommendations about the management of HCC. Since then, new data have emerged in the literature, prompting the governing board of SBH to sponsor a single-topic meeting in August 2018 in São Paulo. All the invited experts were asked to make a systematic review of the literature reviewing the management of HCC in subjects with cirrhosis. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of updated recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present manuscript is the final version of the reviewed manuscript containing the recommendations of SBH.

Background and rationale: Many different non-invasive methods have been studied with the purpose of staging liver fibrosis. The objective of this study was verifying if transient elastography is superior to aspartate aminotransferase to platelet ratio index for staging fibrosis in patients with chronic hepatitis C. Material and methods: A systematic review with meta-analysis of studies which evaluated both non-invasive tests and used biopsy as the reference standard was performed. A random-effects model was used, anticipating heterogeneity among studies. Diagnostic odds ratio was the main effect measure, and summary receiver operating characteristic curves were created. A sensitivity analysis was planned, in which the meta-analysis would be repeated excluding each study at a time. Results: Eight studies were included in the meta-analysis. Regarding the prediction of significant fibrosis, transient elastography and aspartate aminotransferase to platelet ratio index had diagnostic odds ratios of 11.70 (95% confidence interval = 7.13-19.21) and 8.56 (95% confidence interval = 4.90-14.94) respectively. Concerning the prediction of cirrhosis, transient elastogra-phy and aspartate aminotransferase to platelet ratio index had diagnostic odds ratios of 66.49 (95% confidence interval = 23.71-186.48) and 7.47 (95% confidence interval = 4.88-11.43) respectively. Conclusion: In conclusion, there was no evidence of significant superiority of transient elastography over aspartate aminotransferase to platelet ratio index regarding the prediction of significant fibrosis, but the former proved to be better than the latter concerning prediction of cirrhosis.

Background and Aims. The presence of dermatologic reaction as an adverse event to sorafenib treatment in patients with unre-sectable hepatocellular carcinoma has been indicated as a prognostic factor for survival in a recent prospective analysis. To date, this is the only clinical predictor of treatment response, which can be evaluated earlier in the treatment and, therefore, contribute to a better and more individualized patient management.Material and methods. This retrospective study included 127 patients treated with sorafenib under real-life practice conditions in two hepatology reference centers in Brazil. Demographic data, disease/medical history and time of sorafenib administration as well as adverse events related to the medication were recorded in a database.Results. Cirrhosis was present in 94% of patients, 85.6% were Child-Pugh A, 80.3%BCLC-C, 81% had vascular invasion and/or ext-rahepatic spread and 95% had a performance status 0 to 1.The median duration of treatment was 10.1 months (range: 0.1-47 months).The most common adverse event within the first 60 days of treatment were diarrhea (62.2%) and dermatological reaction (42%).The median overall survival for the cohort was 20 months, and it was higher for patients who developed dermatological reactions within the first 60 days compared to those who did not present this adverse event.Conclusion. This retrospective analysis showed the use of sorafenib in patients selected according to BCLC staging, and it is the first external validation of early dermatolog-ic adverse events as a predictor of overall survival in patients with advanced hepatocellular carcinoma.

Renal failure in cirrhotic patients is a very severe condition. Hepatorenal syndrome has the worst prognosis among all causes of kidney failure in such patients. Hepatorenal syndrome is diagnosed especially in cirrhotic patients with ascites who develop loss renal function, despite diuretic suspension and volume expansion with albumin and for whom other causes of kidney injury have been excluded. Patients with hepatorenal syndrome should be treated with a vasoconstrictor in combination with albumin as a bridge to receiving a liver transplant. The vasoconstrictor of choice is terlipressin or noradrenaline. In spite of higher drug-related costs associated to terlipressin, initial evidence demonstrates that, considering all direct medical costs involved, the treatment strategy using terlipressin is probably more economical than that using noradrenaline.

Chronic infection by hepatitis C virus (HCV) is one of the main risk factors for the development of liver cirrhosis and hepatocellular carcinoma. However, the emergence of hepatocellular carcinoma (HCC) in non-cirrhotic HCV patients, especially after sustained virological response (SVR) is an unusual event. Recently, it has been suggested that HCV genotype 3 may have a particular oncogenic mechanism, but the factors involved in these cases as well as the profile of these patients are still not fully understood. Thus, we present the case of a non-cirrhotic fifty-year-old male with HCV infection, genotype 3a, who developed HCC two years after treatment with pegylated-interferon and ribavirin, with SVR, in Brazil.

ABSTRACT BACKGROUND - Variceal bleeding has a high mortality among cirrhotics, and screening with endoscopy is indicated at the diagnosis of cirrhosis. Screening with endoscopy implies discomfort, risks and considerable costs. OBJECTIVE - To evaluate platelet count squared/spleen diameter-aspartate aminotransferase ratio (PS/SA), as a non-invasive predictor of esophageal varices in cirrhotics. METHODS - This cross-sectional study evaluated cirrhotics for PS/SA and presence of esophageal varices. Outpatient records of cirrhotic patients were reviewed for the abovementioned data. Sensitivity, specificity, negative and positive predictive values of PS/SA were calculated. After the univariate analysis, variables with P

PURPOSE: To evaluated the effects of L-arginine (a NO donor) and L-NAME (Nw-nitro-L-arginine methyl ester - a NOS inhibitor) on ischemia-reperfusion in rat livers.METHODS: One hundred fifty two male Wistar rats were divided into four groups: control (simulated surgery); hepatic IR; pretreatment with L-arginine plus hepatic IR; and L-NAME plus hepatic IR. The hepatocellular damage was evaluated at the first, third and seventh days after the procedures through the alanine-aminotransferase (ALT) and aspartate-aminotransaminase (AST) levels, as well as histopathological features: vascular congestion (VC); steatosis (STE); necrosis (NEC); and inflammatory infiltration (INF). The mortality rate was also evaluated.RESULTS: The pretreatment with L-NAME significantly worsened the AST levels after hepatic IR (p

ABSTRACT Since the publication of the Brazilian Association of Hepatology recommendations for the prevention and treatment of variceal bleeding in 2010, new evidence-based data were reported in the literature. This has changed our current management for portal hypertension. This review updates the previous recommendations. It takes the new prognostic staging of cirrhosis into account allowing tailored treatment for advanced fibrosis, compensated or decompensated cirrhosis. An organizing panel of five experts reviewed all recommendations according to available data, which were subsequently scrutinized by all members of the Brazilian Association of Hepatology using a web-based approach. The accepted recommendations are presented in this manuscript.

Non-alcoholic fatty liver disease (NAFLD) is defined as a spectrum of liver diseases ranging from simple steatosis to steatohepatitis (NASH). Alterations in intestinal microbiota and inflammatory response may play a key role in disease progression and development of complications in liver diseases, mainly in cirrhosis and NASH. The aim of this study was to perform a systematic review on randomized clinical trials (RCTs) testing probiotics, prebiotics or both (synbiotics) in the treatment of NAFLD in adult patients. After the screening process, 9 full-text articles were included in the review and 6 studies were excluded. Three randomized controlled trials were finally included in the qualitative synthesis. All patients in all the 3 studies were randomized to receive different formulations of probiotics, synbiotics or placebo. Reductions in aminotransferases were observed in the treated group in 2 of the studies. However, in one study reductions were also detected in the control group. In conclusion, the available evidence precludes, for the moment, recommendations on the use of pre and probiotics in clinical practice.

Context Transplantation is the only cure for decompensated cirrhosis. Model for End-Stage Liver Disease (MELD) is used in liver allocation. Objectives Comparing survival of enlisted populations in pre- and post-MELD eras and estimating their long-term survival. Methods This is a retrospective study of cirrhotics enlisted for transplantation during pre- and post-MELD eras. Survival curves were generated using Kaplan-Meier’s model. Cox’s model was used to determine risk factors for mortality. Exponential, Weibull’s, normal-log and Gompertz’s models were used to estimate long-term survival. Results The study included 162 patients enlisted in pre-MELD era and 184 in post-MELD period. Kaplan-Meier’s survival curve of patients enlisted in post-MELD era was better than that of pre-MELD period (P = 0.009). This difference remained for long-term estimates, with a survival of 53.54% in 5 years and 44.64% in 10 years for patients enlisted in post-MELD era and of 43.17% and 41.75% for pre-MELD period. Era in which patients had been enlisted (P = 0.010) and MELD score at enlistment (P

Background & Aims. Variceal bleeding is a dramatic and common complication of cirrhosis, and, therefore, endoscopy is recommended for the screening of EV (esophageal varices) in every cirrhotic. This study evaluates the capacity of APRI (aspartate aminotransferase-to-platelet ratio index) in non-invasively predicting EV.Material and methods. This cross-sectional study evaluated cirrhotics for their APRI value and the presence of EV, with a cutoff point of 1, 3; platelet count, spleen diameter, PC/SD (platelet count/ spleen diameter ratio), aspartate aminotransferase/alanine aminotransferase ratio, Child-Pugh score and MELD (model for end-stage liver disease) score were also studied.Results. The study included 164 cirrhotics, 59.7% male, with a mean age of 56.7 years. APRI demonstrated a sensitivity of 64.7% (95% confidence interval-95%CI = 0.56-0.73), specificity of 72.7% (95%CI = 0.59-0.86), positive predictive value of 86.5% (95%CI = 0.79-0.94), negative predictive value of 43.2% (95%CI = 0.32-0.55). In the univariate analysis, platelet count, spleen diameter, Child and MELD scores, PC/SD and APRI were related to EV (p < 0.05). In the logistic regression, only platelet count and Child score were associated to EV (p < 0.05).Conclusion. APRI is not an independent factor for the prediction of EV. Its sensitivity, specificity and predictive values are insufficient for the index to be used for the screening of EV in cirrhotics.

Context Hepatitis B virus (HBV) can cause fulminant hepatitis, cirrhosis and hepatocellular carcinoma, and is one of the most common causes of acute and chronic liver failure. The genetic variants of HBV can be decisive for the evolution of these diseases as well as for the election of therapy. Objectives The aim of this study was to evaluate and standardize an in house methodology based on the analysis of the melting curve polymerase chain reaction (PCR) of real-time (qPCR) to screen for genotypes A, D and F of HBV in patients from a hospital in Rio Grande do Sul, Brazil. Methods We evaluated 104 patients presumably with HBV chronic infection. Viral DNA was extracted from plasma and viral genotypes and different mutations were determined using PCR-based protocols. Results A PCR-based methodology was standardized for the analysis of genotypes A, D and F of HBV. The technique was based in a nested PCR with the final step consisting of a multiplex real-time PCR, using the melting curve as a tool for the differentiation of fragments. A higher frequency of genotype D (44.4%), followed by genotype A (22.2%) and genotype F (3.7%) was observed. Conclusion The standardized assay, a nested PCR-multiplex qPCR using specific primers, provides a rapid and accurate method for the differentiation of HBV genotypes that are more frequent in Southern Brazil – A, D and F. This method can be applied in the clinical practice.

CONTEXT: In about 10% of patients with chronic liver disease, it is not possible to identify an etiologic factor. These cases are called cryptogenic cirrhosis. Currently, nonalcoholic steatohepatitis (NASH) is being considered as a possible etiologic factor for a significant segment of patients that presents with cryptogenic cirrhosis. OBJECTIVE: To estimate the prevalence of risk factors for NASH in patients with cryptogenic cirrhosis, in order to verify if there is a causal relationship between them. METHOD: Cross-sectional study, with evaluation of the demographic and laboratorial data of patients with cryptogenic cirrhosis. They were compared with data obtained from a group with NASH and a group with alcoholic and/or hepatitis C (HCV) cirrhosis. RESULTS: Forty seven patients with cryptogenic cirrhosis were evaluated, 47 with NASH and 196 with HCV and/or alcoholic cirrhosis. The mean age of patients with cryptogenic cirrhosis was 52 years, while in those with NASH it was 46.4 years (P = 0,041). The group with cryptogenic cirrhosis had 23 female and 24 male patients. Of the patients who presented with NASH, 68.1% were female. Of the patients who presented with alcoholic/HCV cirrhosis, 64.8% were male. There were no statistically significant differences between the groups. In cryptogenic cirrhosis patients, the following prevalences could be observed: impaired fasting glycemia - 68.2%; obesity - 27.5%; total hypercholesterolemia - 27.9%; low HDL levels - 58.1% (women - 81%; men - 36.4%); hypertriglyceridemia - 16.3%. The results seen in cryptogenic cirrhosis patients showed statistical similarity with the results of the NASH group regarding fasting glycemia (62.8%) and male HDL levels (53.8%). The comparison with the alcoholic/HCV cirrhosis group showed statistical differences regarding fasting glycemia (45.2%), hypercholesterolemia (13.3%) and female HDL levels (50.8%). CONCLUSIONS: It is not possible to establish a causal relationship between cryptogenic cirrhosis and NASH. Only data related to fasting glycemia and HDL levels in male patients showed statistical similarities between both groups of patients.CONTEXTO: Em aproximadamente 10% dos pacientes com doença hepática crônica não é possível identificar um fator etiológico, sendo então rotulados como tendo cirrose criptogênica. Atualmente a esteatohepatite não-alcoólica (EHNA) tem sido considerada como provável etiologia em parcela significativa desses pacientes. OBJETIVO: Estimar a prevalência de fatores de risco para EHNA em pacientes com cirrose criptogênica com o intuito de verificar uma possível relação causal entre as duas doenças. MÉTODOS: Estudo transversal em que foi avaliado o registro de dados demográficos e laboratoriais de pacientes com cirrose criptogênica com a finalidade de compará-los com aqueles obtidos de um grupo de pacientes com EHNA e de um grupo controle composto de cirróticos por hepatite C (HCV) e/ou álcool. RESULTADOS: Foram avaliados 47 pacientes com cirrose criptogênica, 47 com EHNA e 196 com cirrose por HCV e/ou álcool. A média de idade dos pacientes com cirrose criptogênica foi 52 anos, enquanto a daqueles com EHNA foi 46,4 anos (P = 0,041). No grupo com cirosse criptogênica havia 23 mulheres e 24 homens. Naqueles com EHNA predominou o gênero feminino (68,1%) e nos cirróticos por HCV e/ou álcool predominou o gênero masculino (64,8%), sem diferença estatística entre os grupos. Naqueles com cirrose criptogênica, a prevalência de glicemia de jejum alterada foi 68,2%; obesidade, 27,5%; hipercolesterolemia total, 27,9%; baixos níveis de HDL, 58,1% (81% nas mulheres e 36,4% nos homens); e hipertrigliceridemia, 16,3%. A comparação com dados observados nos pacientes com EHNA mostra semelhança estatística entre o perfil glicêmico (62,8%) e níveis de HDL nos homens (53,8%). A comparação com os cirróticos relacionados ao HCV e/ou álcool mostra diferença estatística no perfil glicêmico (45,2%), colesterol total (13,3%) e HDL nas mulheres (50,8%). CONCLUSÃO: Não foi possível estabelecer uma relação causal entre a EHNA e a cirrose criptogênica. Apenas o perfil glicêmico e os níveis de HDL colesterol nos pacientes masculinos apresentaram semelhanças estatísticas entre os dois grupos de doentes.

Background & Aims: An increased frequency of infections by multiresistant bacteria has been described in hospitalized patients. The aim of this study was to evaluate the bacterial resistance profile in cirrhotic patients. Methods: This is a retrospective observational study. We assessed the antimicrobial susceptibility of 5,839 bacterial isolates from patients with and without cirrhosis. Regarding the multidrug resistance, we evaluated 4,505 bacterial isolates from 2,180 patients. Results: Two hundred and fifty-one patients had cirrhosis (mean age 57.6 ± 11 years; 61.8% were male, 47.8% of cases associated with hepatitis C virus). Of the isolates of patients with and without cirrhosis, 174/464 (37.5%) and 1,783/4,041 (44.1%) were multiresistant, respectively (p = 0.007). E. coli was the most common multiresistant bacteria in both groups. Approximately 20% of E. coli and Klebsiella sp. isolates were ESBL-producers and 44% of S. aureus isolates were methicillin-resistant in cirrhotic patients. In cirrhotic patients admitted to the emergency department, hospital ward, and intensive care unit, 28.3%, 50% and 40% had multiresistant isolates, respectively. In patients with and without cirrhosis, 36.2% and 33.5% of isolates were resistant to third-generation cephalosporins, respectively. Conclusions: The empirical treatment of infections in hospitalized patients using broad-spectrum antibiotics should consider the observed pattern of bacterial resistance.

Although the protease inhibitors have revolutionized the therapy of chronic hepatitis C (CHC), the concomitant use of pegylated-interferon (PEG-IFN) and ribavirin (RBV) is associated to a high rate of adverse effects. In this study, we evaluated the consequences of PEG-IFN and RBV and their relationship with mortality in patients with cirrhosis. METHODS: Medical records of CHC who underwent treatment with PEG-IFN and RBV in a public hospital in Brazil were evaluated. All the patients with cirrhosis were selected, and their clinical and laboratory characteristics, response to treatment, side effects and mortality were evaluated. RESULTS: From the 1,059 patients with CHC, 257 cirrhotic patients were evaluated. Of these, 45 (17.5%) achieved sustained viral response (SVR). Early discontinuation of therapy occurred in 105 (40.8%) patients, of which 39 (15.2%) were due to serious adverse effects. The mortality rate among the 257 cirrhotic patients was 4.3%, occurring in 06/242 (2.4%) of the Child-A, and in 05/15 (33.3%) of the Child-B patients. In conclusion, the treatment of patients with cirrhosis due to HCV with PEG-IFN and RBV shows a low SVR rate and a high mortality, especially in patients with liver dysfunction.

Liver biopsy is the gold standard method for the grading and staging of chronic viral hepatitis, but optimal biopsy specimen size remains controversial. The aim of this study was to evaluate the quality of liver specimen (number of portal tracts) and to evaluate the impact of the number of portal tracts in the staging of chronic hepatitis. Material and Methods: 468 liver biopsies from consecutive patients with hepatitis C virus and hepatitis B virus infection from 2009 to 2010 were evaluated. Results: The length of fragment was less than 10 mm in 43 cases (9.3%), between 10 and 14 mm in 114 (24.3%), and ≥ 15 mm in 311 (64.4%); of these, in 39 (8.3%) cases were ≥ 20 mm. The mean representation of portal tracts was 17.6 ± 2.1 (5-40); in specimens ≥ 15 mm the mean portal tract was 13.5 ± 4.7 and in cases ≤ 15 mm was 11.4 ± 5.0 (p = 0.002). Cases with less than 11 portal tracts were associated with F3, and cases with 11 or more portal tracts with F2 (p = 0.001). Conclusion: this study demonstrated the good quality of liver biopsy and a relationship between the macroscopic size of the fragment and the number of portal tracts.

Introduction. Considering the high prevalence of liver tumors and the impact on patient survival, a greater understanding of the biological behavior of those tumors if of great importance. The multidrug resistance gene (MDR1) may present as single nucleotide polymorphism (SNP) which can affect the expression and activity of P-glycoprotein (Pgp), and high expression of Pgp has been associated with a worse prognosis in affected patients.Objective. To correlate the C3435T polymorphism in the MDR1 gene with the immunohistochemical expression of Pgp.Material and methods. A total of 67 samples from patients with diagnosis of hepatocellular carcinoma (HCC), collected in the period from 2000 to 2009, were analyzed. The polymorphism in the MDR1 gene was determined by the technique of allele-specific real time PCR using TaqMan assay, and the expression of protein Pgp was evaluated by immunohistochemistry.Results. Among the samples evaluated, 56 (83.6%) were from male patients and 11 (16.4%) from females. Mean age was 60.6 years (± 8.8), ranging from 37 to 85 years. The etiology of the HCC was related to hepatitis C virus infection (HCV) in 31 (46.3%) of cases, followed by hepatitis C virus infection + alcohol in 24 cases (35.8%), alcohol in 4 cases (6)%, hepatitis B virus (HBV) in 4 cases (6%) and other factors in 4 cases (6%). Liver transplantation was performed in 48 cases (71.6%) and hepatectomia in 19 cases (28.4%). The genotypes CC, CT and TT showed frequencies of 25.4%, 41.8% and 32.8%, respectively, and the allele frequencies were 46.3% for allele C and 53.7% for allele T. The expression of Pgp in over 75% of the cells was significantly more frequent in tumor tissue. On the other hand, a low expression of Pgp, in less than 25% of the cells, was significantly more frequent in non-tumor tissue. The Pgp expression in more than 50% of tumor cells of individuals with genotypes CC, CT and TT was 15.7%, 51.0% and 33.3%, respectively, and was significantly higher when in the presence of allele T (p = 0.002).Conclusion. The presence of the polymorphic allele T is related to increased expression of Pgp protein in patients with HCC.

CONTEXT: Chronic hepatitis C as well as non-alcoholic fatty liver disease are recognized as the main cause of liver disease in Western countries. It is common to see the concomitance of the diseases and the influence of steatosis in the sustained virological response of patients with hepatitis C virus. OBJECTIVE: Assess the sustained virological response in chronic hepatitis C patients according to the presence of liver steatosis. METHODS: One hundred sixty patients with chronic hepatitis C were retrospectively evaluated. Demographic data such as gender, age, body mass index, presence of diabetes mellitus and systemic arterial hypertension, virus genotype and use of pegylated interferon were analyzed, as was the staging of fibrosis and the presence of steatosis at histology. RESULTS: Most patients were male (57.5%), with a mean age of 48 ± 9.7 years. The most frequent genotype observed was 3 (56.9%) and, in the histological evaluation, steatosis was observed in 65% of the patients (104/160). Sustained virological response in patients with steatosis occurred in 38.5%, and in 32.1% in patients without steatosis (P = 0.54). When we analyzed possible factors associated with the presence of steatosis, only body mass index and systemic arterial hypertension revealed a significant association. When the factors that influenced sustained virological response were evaluated in a logistic regression, genotype and use of pegylated interferon proved to be independent factors associated to the response. CONCLUSION: In the evaluated patients the presence of liver steatosis did not influence the sustained virological response of patients with chronic hepatitis C treated with interferon and ribavirin.

CONTEXT: Upper gastrointestinal bleeding associated to esophageal varices is the most dramatic complication of cirrhosis. It is recommended screening every cirrhotic for esophageal varices with endoscopy. OBJECTIVES: To evaluate the capacity of the platelet count/spleen diameter ratio in non-invasively predicting esophageal varices in a population of cirrhotics originated in an independent center from the one in which it was developed. METHODS: The study included patients from the ambulatory care clinic of cirrhosis of a Brazilian hospital and studied platelet count, spleen diameter and presence of esophageal varices, as well as Child and MELD scores. It used a cutoff value of 909 for the platelet count/spleen diameter ratio, as previously published. A sample of 139 patients was needed to grant results a 95% confidence level. RESULTS: The study included 164 cirrhotics, 56.7% male, with a mean age of 56.6 ± 11.6 years. In the univariate analysis, platelet count, spleen diameter, presence of ascites, Child and MELD scores and the platelet count/spleen diameter ratio were related to esophageal varices (PCONTEXTO: Hemorragia digestiva por varizes esofágicas é a complicação mais dramática da cirrose. É recomendada triagem de varizes esofágicas em todo o cirrótico. OBJETIVO: Avaliar o índice de contagem de plaquetas/diâmetro do baço como predição de varizes esofágicas em uma população distinta daquela em que ele foi desenvolvido. MÉTODOS: O estudo incluiu pacientes do ambulatório de cirrose de um hospital brasileiro quanto ao número de plaquetas, diâmetro ecográfico do baço, presença de varizes esofágicas, Child e MELD. O ponto de corte do índice foi de 909. Amostra de 139 pacientes foi estimada para conferir nível de confiança de 95%. RESULTADOS: Incluíram-se 164 cirróticos, 56,7% homens e com média de idade de 56,6 anos. Na análise univariada, número de plaquetas, diâmetro do baço, ascite, Child, MELD e o índice de contagem de plaquetas/diâmetro do baço relacionaram-se às varizes esofágicas (P

In the last decades, several improvements in the management of variceal bleeding have resulted in a significant decrease in morbidity and mortality of patients with cirrhosis and bleeding varices. Progress in the multidisciplinary approach to these patients has led to a better management of this disease by critical care physicians, hepatologists, gastroenterologists, endoscopists, radiologists and surgeons. In this respect, the Brazilian Society of Hepatology has, recently, sponsored a consensus meeting in order to draw evidence-based recommendations on the management of these difficult-to-treat subjects. An organizing committee comprised of four people was elected by the Governing Board and was responsible to invite 27 researchers from distinct regions of the country to make a systematic review of the subject and to present topics related to variceal bleeding, including prevention, diagnosis, management and treatment, according to evidence-based medicine. After the meeting, all participants met together for discussion of the topics and the elaboration of the aforementioned recommendations. The organizing committee was responsible for writing the final document. The meeting was held at Salvador, May 6th, 2009 and the present manuscript is the summary of the systematic review that was presented during the meeting, organized in topics, followed by the recommendations of the Brazilian Society of Hepatology.Vários avanços científicos obtidos nas últimas duas décadas foram incorporados no manejo da hemorragia digestiva alta varicosa, levando a uma redução significante da sua morbimortalidade, atribuída à abordagem multidisciplinar do sangramento varicoso por paramédicos, emergencistas, intensivistas, gastroenterologistas, hepatologistas, endoscopistas, radiologistas intervencionistas e cirurgiões. Recentemente, a Sociedade Brasileira de Hepatologia patrocinou uma reunião de consenso, visando o estabelecimento de recomendações nacionais, sobre o manejo da hemorragia digestiva alta varicosa, incluindo sua prevenção, diagnóstico e tratamento, de acordo com a melhor evidência científica disponível. A diretoria da Sociedade Brasileira de Hepatologia elegeu quatro membros para a comissão organizadora que, por sua vez, convidou 27 pesquisadores de diferentes regiões do país, para realizar uma revisão sistemática sobre tópicos relacionados ao manejo hemorragia digestiva alta varicosa. A reunião de consenso ocorreu em Salvador, BA, em 6 de março de 2009. Após o encontro, todos os participantes se reuniram para elaboração das recomendações, cuja redação ficou sob a responsabilidade da comissão organizadora. O presente artigo descreve as recomendações da Sociedade Brasileira de Hepatologia sobre o manejo do sangramento associado à hipertensão portal, divididas em módulos e precedidas por resumo das apresentações realizadas na reunião de consenso.

CONTEXTO: A hipertensão portal exerce papel importante na patogênese da ascite. OBJETIVO: Avaliar o gradiente de pressão venosa hepática e a presença de ascite em pacientes com cirrose. MÉTODOS: Foram estudados 83 pacientes com cirrose. Todos os doentes realizaram estudo ecográfico para a identificação de ascite e foram submetidos a estudo hemodinâmico hepático para determinação do gradiente de pressão venosa hepática. RESULTADOS: Na população avaliada, observou-se ascite em 70 doentes (84,3%), sendo que a média geral do gradiente de pressão venosa hepática foi de 15,26 ± 6,46 mm Hg. Não houve diferença estatisticamente significante (P = 0,061) quando avaliadas as médias do gradiente de pressão venosa hepática nos pacientes com (14,70 ± 6,43 mm Hg) e sem ascite (18,64 ± 5,78 mm Hg). Ao ser utilizado nível de corte de 8 mm Hg, para se avaliar o risco do desenvolvimento de ascite, observou-se que nos pacientes que apresentaram o gradiente de pressão venosa hepática superior a 8 mm Hg, o risco relativo do desenvolvimento de ascite foi de 0,876 (0,74-1,03), P = 0,446. CONCLUSÃO: Nível pressórico de 8 mm Hg, determinado pelo gradiente de pressão venosa hepática, não define a presença ou ausência de ascite no paciente cirrótico e, tendo em vista a similitude das médias de pressão dos pacientes com e sem derrame peritonial, não se pode definir um ponto de corte para o surgimento de tal complicação.CONTEXT: Portal hypertension plays an important role in the pathogenesis of ascites. OBJECTIVES: To evaluate the hepatic venous pressure gradient and the presence of ascites in cirrhotic patients. METHODS: Eighty-three patients with cirrhosis were evaluated. All of the patients were submitted to ultrasonography to identify ascites and to a hepatic hemodynamic investigation to determine the hepatic venous pressure gradient. RESULTS: In the population evaluated, ascites was observed in 70 patients (84.3%), and the mean hepatic venous pressure gradient was 15.26 ± 6.46 mm Hg. There was no statistically significant difference (P = 0.061) between the means of hepatic venous pressure gradient in patients with (14.70 ± 6.43 mm Hg) and without ascites (18.64 ± 5.78 mm Hg). When using a cut-off point of 8 mm Hg in order to assess the risk of developing ascites, patients with hepatic venous pressure gradient above 8 mm Hg were found to have a relative risk of 0.876 (CI = 0.74-1.03), (P = 0.446) of progressing to ascites. CONCLUSIONS: The pressure level of 8 mm Hg, as determined by the hepatic venous pressure gradient, does not define the presence or absence of ascites in the cirrhotic patient, and in view of the similarity between mean pressures in patients with or without peritoneal effusion, it is impossible to define a cut-off point for the emergence of such complication.

Background. The most important factors to predict the sustained virological response (SVR) are the genotype and the fibrosis grade, although there are other predictive factors to be considered, mainly in HCV/ HIV coinfected patients.Aim. To evaluate different prognostic factors to obtain the SVR in HCV monoin-fected and HCV/HIV coinfected genotype I patients emphasizing the type of early virological response (EVR)-complete or partial.Methods. This is a cohort study, retrospective, where the registers of HCV mo-noinfected or HCV/HIV coinfected patients, genotype I, treated with pegylated interferon + ribavirin were reviewed. The prognostic factors: age greater than 40 years, viral load higher than 600,000UI/mL, and fibrosis grade (score METAVIR) were evaluated pre-treatment, and also the EVR considering the reduction of 100 times of the basal viral load (partial EVR) or negative PCR (complete EVR) in the week 12. In the statistical analysis, multivariate analysis was used. The significance level adopted was 5%.Results. There were 323 HCV monoinfected and 59 HCV/HIV coinfected. The SVR was 35.3% in monoinfected and 23% in coinfec-ted patients. The worst results was observed in those with age greater than 40 years, high viral load, pronounced fibrosis (F4) and partial EVR, with an expected probability of 1.9% for SVR in those coinfected and 3.8% in monoinfected. In conclusion, patients with cirrhosis HCV genotype 1, age greater than 40 years, high viral load, coinfected with HIV or not, will present a low SVR if did not obtain negative PCR in week 12, and should be evaluated for discontinuation.

CONTEXT: No effective treatment is available for nonalcoholic steatohepatitis in nowadays. OBJECTIVES: To develop a model of nonalcoholic steatohepatitis induced by a methionine and choline deficient diet, as well as to evaluate the role of metformin, vitamin E and simvastatin in the nonalcoholic steatohepatitis progression. METHODS: The study analyzed prospectively 50 Wistar rats for a 90-day period and divided them into five groups of 10 rats. One group was given standard rat diet and the others received the methionine and choline deficient diet. Among the four groups that received this diet, one received saline 0,9% and the others received metformin, vitamin E or simvastatin. After the study period, the animals were sacrificed and their blood was collected for biochemical analysis. The livers were removed for lipoperoxidation analysis and for the histological examinations. RESULTS: The methionine and choline deficient diet was able to induce steatosis in 100% of the animals and nonalcoholic steatohepatitis in 27 (69.2%). The alanine aminotransferase levels were significantly higher in the simvastatin group. The aspartate aminotransferase levels were also higher in the simvastatin group, but were statistically significant only in relation to the standard diet group. When lipoperoxidation values were compared, the groups that received standard rat diet and methionine and choline deficient with vitamin E presented significantly lower rates than the others. The presence of fibrosis was significantly smaller in the group receiving vitamin E. CONCLUSIONS: The diet used was able to induce steatosis and nonalcoholic steatohepatitis. Besides vitamin E showed to reduce the liver oxidative stress, as well as the fibrosis developmentCONTEXTO: Ainda não há um tratamento comprovadamente eficaz para a esteatohepatite não-alcoólica. OBJETIVO: Desenvolver um modelo experimental de esteatohepatite não-alcoólica induzida por dieta deficiente em metionina e colina, bem como avaliar o papel do metformina, da vitamina E e da sinvastatina na evolução da esteatohepatite não-alcoólica. MÉTODOS: Foram estudados prospectivamente 50 ratos da linhagem Wistar, por um período de 90 dias, sendo os mesmos divididos em cinco grupos de 10 ratos. Um grupo recebeu ração convencional e os demais a dieta deficiente em metionina e colina. Dentre os quatro grupos que receberam a dieta, para um foi administrado soro fisiológico e para os demais o metformina, a vitamina E e a sinvastatina. Após o período de estudo os animais foram mortos, sendo colhido sangue para análise bioquímica e removido o fígado para análise da lipoperoxidação através do teste de substâncias reativas ao ácido tiobarbitúrico e para a realização dos exames histológicos. RESULTADOS: A dieta deficiente em metionina e colina foi capaz de induzir esteatose em 100% dos animais enquanto que esteatohepatite não-alcoólica foi diagnosticada em 27 (69,2%). Os níveis da ALT foram significativamente maiores no grupo da sinvastatina. Os níveis de AST também foram maiores no grupo da sinvastatina, mas apenas foram estatisticamente significantes em relação ao grupo da ração. Quando se compararam os valores de lipoperoxidação, os grupos da ração convencional e da vitamina E apresentaram índices significativamente menores que os demais. A presença de fibrose foi significativamente menor no grupo que recebeu a vitamina E. CONCLUSÕES: A dieta utilizada foi capaz de induzir esteatose e esteatohepatite não-alcoólica, sendo que a vitamina E demonstrou reduzir o estresse oxidativo hepático, bem como o desenvolvimento de fibrose

CONTEXT: In recent years the hepatitis B virus (HBV) genotyping has been considered a relevant factor in the natural history of the disease. OBJECTIVE: To determine hepatitis B virus genotypes and its epidemiological and clinical implications, in a cohort of patients in a hospital in Porto Alegre, South of Brazil. Methods - Sixty seven patients with HBV chronic infection markers who were being treated at ''Complexo Hospitalar Santa Casa'', in Porto Alegre, RS, Brazil, were evaluated. Demographic and epidemiological data were collected from these group of patients by following a standard protocol and ALT and HBeAg were determined. The genotypes and subtypes were determined by in-house PCR and, finally, the samples were sequenced. The level of significance used was 5%. RESULTS: The qualitative analysis for HBV-DNA by PCR was positive in 79.1% of the samples (53/67). The genotype was determined in all positive VHB-DNA samples and the genotypes A (34%), D (60.4%) and F (5.4%) as well as the subtypes adw, ayw and adw4 were found. No significant correlation was found between the hepatitis B virus genotypes and demographic variables considered as risk factors for hepatitis B virus infection. There was also no correlation between the genotypes and the serological and laboratory variables related to liver disease. CONCLUSION: We concluded that the most prevalent genotype found was D. However, further studies are needed to allow us to evaluate the implications of genetic variability in the clinical evolution of HBV carriers.CONTEXTO: Nos últimos anos a genotipagem do vírus da hepatite B (VHB) tem sido considerado fator relevante para a história natural da doença. OBJETIVOS: Determinar os genótipos do VHB e suas implicações clínicas e epidemiológicas, em uma coorte de pacientes em um hospital de Porto Alegre, RS, sul do Brasil. MÉTODOS: Foram avaliados 67 pacientes com marcadores de infecção crônica pelo VHB que estavam sendo tratados no Complexo Hospitalar Santa Casa de Porto Alegre, RS. Foi aplicado um protocolo com dados demográficos e epidemiológicos dos pacientes, e AgHBe e ALT foram determinadas. Os genótipos e subtipos foram determinados por PCR in-house e, finalmente, as amostras foram sequenciadas. O nível de significância utilizado foi de 5%. RESULTADOS: A análise qualitativa de VHB-DNA por PCR foi positiva em 79,1% das amostras (53/67). O genótipo foi determinado em todas as amostras de VHB-DNA positivo. A análise demonstrou a presença dos genótipos A (34%), D (60,4%) e F (5,4%). Foram encontrados os seguintes subtipos: adW, ayw e adw4. Nenhuma correlação significativa foi encontrada entre os genótipos do VHB e as variáveis demográficas estudadas como fator de risco para infecção pelo VHB, e com os exames sorológicos e laboratoriais de doença hepática. CONCLUSÃO: O genótipo mais prevalente encontrado foi o D. No entanto, mais estudos são necessários para que se possa avaliar as implicações da variabilidade genética na evolução clínica de portadores do VHB.

Background/aims. No prospective study has been published investigating etiology of HCC in Latin America. The primary aim of this prospective study was to analyze the etiology of liver disease in patients with HCC from our area. Secondary aims were to evaluate staging using Okuda and BCLC classifications; and percentage of patients receiving treatment.Methods. The Governing Board of the Latin American Association for the Study of the Liver designed the protocol. During a 18 month period, all members were invited to load their incident HCC cases on line.Results. 240 cases from 9 countries were uploaded, 174 were male (72.5%), median age was 64 years, interquartile range 57-72. In 85.4% of cases, patients had underlying cirrhosis. Main etiological factors were: HCV in 74 patients (30.8%), alcohol in 49 (20.4%), cryptogenic cirrhosis in 35 (14.6%), HBV in 26 (10.8%), HCV plus alcohol in 14 (5.8%). Considering the combinations, hepatitis C was shown in 91 patients (38%); chronic alcoholism in 68 patients (28%); and hepatitis B in 33 patients (14%). There were no significant differences between the groups in the age at diagnosis. Percentage of male gender was higher in groups of alcohol (94%), HCV plus alcohol (93%) and HBV (85%) than in cryptogenic cirrhosis (60%) and HCV (59%) (p

Background and Rationale. Among the adverse events related to tuberculosis treatment, hepatotoxicity is the most serious, and recognition of risk factors for it is essential to achieve successful therapy. The aim of the study is to evaluate the role of anti-HCV as a risk factor for hepatotoxicity in hospitalized patients under tuberculosis treatment with rifampicin, isoniazid and pyrazinamide (RHZ).Methods. Historical cohort study carried out at Hospital Sanatório Partenon, from 1998 to 2006. Patients aged 18 years or older, tested for anti-HCV, who presented normal pre-treatment aminotransferases (AST, ALT) and bilirrubin and who used RHZ during hospitalization were included in the study. Individuals who used anti-tuberculosis drugs six months prior to hospitalization, had clinical evidence of chronic liver disease or showed previous history of hepatotoxicity to RHZ were excluded.Results. A sample of 534 patients was studied. The incidence of hepatotoxicity was 8.8% (n = 47). After univariate analysis, the following variables were associated to hepatotoxicity: anti-HIV positive, anti-HCV positive, use of antiretroviral therapy and high doses of rifampicin and isoniazid per kg of body weight (p < 0.05). When Cox regression was performed, anti-HIV positive [RR = 2.3 (IC95% 1.2-4.1); p = 0.008] and high doses of isoniazid per kg of body weight [RR = 1.3 (IC95% 1.1-1.7); p = 0.016] remained independently associated to development of hepatotoxicity.Conclusions. In conclusion, the anti-HIV positive and high doses of isoniazid were considered independent risk factors for hepatotoxicity due to RHZ esqueme in the present study. Though univariate analysis showed that anti-HCV was associated to the outcome, it was not identified as an independent risk factor for hepatotoxicity related to the use of RHZ when the analysis was controlled to HIV.

Background/objectives. The study evaluates the outcome of patients who performed orthotopic liver transplantation (LT) as treatment for hepatocellular carcinoma (HCC), with percutaneous ethanol injection (PEI) while on the waiting list, verifying the effectiveness of this treatment in producing tumor necrosis and avoiding dropout and identifying treatment-related complications.Material and methods.Medical records of 97 patients on the waiting list for LT at Hospital Clinic of Barcelona were examined. Sixty-two (56.3%) patients had been treated with PEI (group 1); 35 (31.8%) had not received any anti-tumor therapy before LT (group 2).Results.Complete necrosis of the tumor was observed in 38/59 (64.3%) patients. The presence of additional nodules in the explant and the diameter of the main tumor of group 1 was significantly lower than in group 2 (p = 0.002). Dropout related to tumor progression occurred in 4.8% and 8.5%, and tumor recurrence in 5% and 6.2% for groups 1 and 2, respectively. Major complications were not evidenced after 421 PEI sessions and there was no tumor implant in the needle traject.Conclusions. In conclusion, the percutaneous treatment of HCC with PEI is a safe and effective method before the LT.

CONTEXTO: Tem sido sugerido que os pacientes coinfectados por vírus da hepatite C e da imunodeficiência humana (VHC/HIV) devam ser tratados com interferon peguilado associado à ribavirina (PEG+RBV) porque as taxas de resposta virológica sustentada seriam maiores do que aquelas obtidas com interferon convencional associado à ribavirina (IFN+RBV). No entanto, há escassez de trabalhos na literatura comparando as duas opções de tratamento nesta população de pacientes, em especial fora do cenário de ensaios clínicos. OBJETIVO: Avaliar a resposta virológica sustentada ao tratamento com IFN+RBV versus PEG+RBV em pacientes coinfectados pelo vírus da hepatite C genótipo 1 e vírus da imunodeficiência humana (VHC-1/HIV), no âmbito do programa do Ministério da Saúde. MÉTODOS: Trata-se de estudo de coorte misto, onde foram revisados prontuários de pacientes coinfectados por VHC-1/HIV tratados com IFN+RBV (antes de 2002) ou PEG+RBV (a partir de 2002) pelo período de 48 semanas, no âmbito da Secretaria da Saúde do Estado do Rio Grande do Sul. Foram avaliadas as características demográficas (idade, gênero e peso), contagem de células CD4 e histopatologia - atividade inflamatória (A) e fibrose - segundo classificação METAVIR. O nível de significância adotado na análise estatística foi de 5%. RESULTADOS: Foram avaliados 81 pacientes coinfectados por VHC-1/HIV, 22 que utilizaram IFN+RBV e 59 que utilizaram PEG+RBV por 48 semanas. Os grupos eram semelhantes no que tange à média de idade, gênero, peso, contagem de células CD4 e grau de fibrose. Os pacientes que utilizaram IFN+RBV apresentaram maior atividade histológica com proporção de A2+A3 que superava aqueles que utilizaram PEG+RBV (PCONTEXT: It has been suggested that coinfected patients HCV/HIV must be treated with pegylated interferon associated to ribavirin (PEG+RBV), because of better taxes of sustained virological response when compared to those treated with conventional interferon associated to ribavirin (IFN+RBV). There are few studies in the literature comparing these two treatments options in this population. OBJECTIVE: To evaluate the sustained virological response to the treatment with IFN+RBV versus PEG+RBV in coinfected patients HCV/HIV genotype 1, in a public health program. METHODS: It is a cohort study, where the data of the coinfected patients treated with IFN+RBV (before 2002) or PEG+RBV (from 2002) during 48 weeks in the Brazilian Health Ministry program were reviewed. Demographic characteristics were evaluated (age, gender and weight), CD4 cell count and histopathology - inflammatory activity (A) and fibrosis grade, by METAVIR classification. The significance level adopted was 5%. RESULTS: Eighty one patients were evaluated, 22 treated with IFN+RBV and 59 treated with PEG+RBV. Both were similar relating to age, gender, weight, CD4 cell count and fibrosis grade. Those treated with IFN+RBV presented a greater proportion of A2+A3 patients than those treated with PEG+RBV (P

CONTEXTO: Ainda existem vários aspectos desconhecidos a respeito da esteatohepatite não-alcoólica, principalmente em relação à fisiopatologia e ao seu tratamento medicamentoso. Dessa forma, os modelos experimentais são importante para o melhor entendimento dessa doença, bem como para a avaliação do efeito das drogas. OBJETIVO: Desenvolver um modelo experimental de esteatohepatite não-alcoólica a partir do uso de dieta deficiente em metionina e colina. MÉTODOS: Foram utilizados 50 ratos machos da linhagem Wistar. A dieta deficiente em metionina e colina foi processada de forma artesanal. Um grupo de 40 animais recebeu a dieta durante 90 dias e utilizou-se um grupo controle com 10 ratos que recebeu ração padronizada pelo mesmo período. Após, os animais foram mortos por decapitação e foi realizada laparotomia com hepatectomia total e preparo do material para análise macroscópica e histológica. O nível de significância foi a = 0,05. RESULTADOS: Os ratos que receberam a dieta apresentaram perda significativa de peso, com achados de desnutrição e todos mostraram, pelo menos, algum grau de esteatose macrovesicular. O diagnóstico de esteatohepatite não-alcoólica foi realizado em 27 (70%) dos 39 ratos que receberam a dieta. Nenhum dos 10 ratos que recebeu ração apresentou alterações histológicas. CONCLUSÃO:A dieta com restrição de metionina e colina desenvolvida apresenta índices elevados de indução de esteatose e esteatohepatite em modelo animal com baixo custo.CONTEXT: There are still many unknown aspects about nonalcoholic steatohepatitis, especially regarding its pathophysiology and pharmacological treatment. Thus, experimental models are important for a better understanding of this disease and the evaluation of the effects of drugs. OBJECTIVE: To develop a model of experimental nonalcoholic steatohepatitis from use of methionine and choline deficient diet. METHODS: Fifty Wistar male rats were studied. A methionine and choline deficient diet has been processed in a craft. A group of 40 animals received the deficient diet for 90 days, and a group of 10 rats (control group) received the standardized ration in the same period. After, the animals were killed by decapitation, and laparotomy was performed. Hepatectomy was performed and the liver was studied by macroscopy and microscopy. The level of significance considered was of 0,05. RESULTS: The rats that received the deficient diet showed significant loss of weight with findings from malnutrition and all of them had at least some degree of macrovesicular steatosis. The diagnosis of nonalcoholic steatohepatitis was performed in 27 (70%) of the 39 rats that received this deficient diet (1 rat died during the study). None of the 10 rats that received the standardized diet had histological abnormalities. CONCLUSION: The diet restricted in methionine and choline induced steatosis and steatohepatitis in an animal model with low cost.

RACIONAL: O carcinoma hepatocelular é uma complicação que acomete pacientes que apresentam cirrose hepática. A ressecção hepática, o transplante ortotópico de fígado e a ablação percutânea constituem opções terapêuticas com o intuito curativo. OBJETIVO: Avaliar os resultados da ressecção hepática para o tratamento do carcinoma hepatocelular, em fígados cirróticos, em um hospital geral. MÉTODOS: Foram avaliadas as características clínicas, laboratoriais, endoscópicas e histopatológicas de 22 pacientes submetidos a ressecção hepática entre os anos de 1996 e 2005, com o intuito de se avaliar a sobrevida, a identificação de fatores prognósticos e a incidência de recidiva tumoral. Para tanto, especial atenção foi dada aos níveis séricos de bilirrubinas e alfa-fetoproteína, grau de disfunção hepatocelular (avaliado pelas classificações Child-Pugh-Turcotte e " Model for End-Stage Liver Disease" - MELD), tamanho e número de tumores, invasão microvascular e presença de lesões satélites. O nível de significância utilizado foi de 95% na análise estatística. RESULTADOS: A média de idade dos pacientes estudados foi de 62,09 anos, sendo 17 do sexo masculino. Em 10 casos a cirrose hepática esteve associada à infecção crônica pelo vírus da hepatite C, em 4 à combinação do uso crônico do etanol e vírus da hepatite C, em 3 ao vírus da hepatite B, em 2 ao uso do etanol isoladamente, em 1 com uso de medicamentos e, em 2 casos, não foi identificada a causa. Dezoito pacientes apresentaram tumor único, sendo que em 11 o tumor media menos que 5 cm. A sobrevida variou entre 10 dias e 120 meses, com média de 33,5 meses. No final do 1º, 3º e 5º anos, identificou-se sobrevida de 61,90%, 16,67% e 11,11%, respectivamente. Houve três óbitos nos primeiros 3 meses posteriores à ressecção hepática. Treze óbitos foram identificados após os primeiros 3 meses, sendo que 12 casos foram relacionados à recidiva e progressão da neoplasia. Um paciente faleceu no período pós-operatório imediato de novo procedimento cirúrgico para ressecção de uma recidiva tumoral. No que se refere à sobrevida e à identificação de fatores prognósticos, foi identificada relação entre sobrevida e invasão microvascular. Não foi observada diferença, com significância estatística, nas curvas de sobrevida entre os níveis séricos de bilirrubinas e alfa-fetoproteína, grau de disfunção hepatocelular, tamanho e número de lesões. Entretanto, foi identificada probabilidade de recidiva tumoral maior no grupo de pacientes que apresentava invasão microvascular no estudo histopatológico. CONCLUSÃO: Apesar do pequeno número de pacientes estudados, observaram-se maus resultados com o tratamento cirúrgico do carcinoma hepatocelular. A seleção adequada dos casos pode ser fator importante para a melhoria desse resultado.BACKGROUND: The hepatocellular carcinoma is a disorder that affects patients suffering from cirrhosis. Liver resection, orthotopic liver transplantation and percutaneous ablation are some forms of therapy currently used to provide a cure for this disease. AIM: To assess the results achieved through liver resection for the treatment of the hepatocellular carcinoma in patients with cirrhosis being under treatment in a general hospital. METHODS: Clinical observation, laboratory test results, endoscopic and histopathologic analysis were taken into consideration in the case of 22 patients who underwent liver resection between 1996 and 2005. To verify the survival rates, identify the prognostic factors and determine the risk of recurrence, special attention was given to the serologic levels of bilirubins and alpha-fetoprotein, and to the level of the hepatocellular dysfunction (classified according to the Child-Pugh-Turcotte and the Model for End-Stage Liver Disease parameters). The size and number of tumours, microvascular invasion and the presence of satellite lesions were also taken into consideration. The level of statistic significance employed was of 95%. RESULTS: In the cases studied, patients had an average age of 62.09 years, being 17 of them male. In 10 cases the liver cirrhosis was associated to the hepatitis C chronic infection; in 4 cases there was a combination of chronic ingestion of ethanol and the hepatitis C virus; in 3 cases there was an association with the hepatitis B virus chronic infection. Two cases were related to the chronic ingestion of ethanol alone and in one case the use of medications was reported. It was not possible to establish the etiology in two of the cases studied. Eighteen patients had a single tumour, 11 of them smaller than 5 cm. The survival rate varied between 10 days and 120 months, being of 33.5 months on average. At the end of the 1st, 3rd and 5th year, the survival rates were 61.90%, 16.67% and 11.11%, respectively. Three patients died within the first 3 months after the liver resection. Thirteen patients died after the first 3 months, 12 of the cases associated to tumour recurrence and tumour progression. There was one death in the immediate post-operative period of a second operation carried out to remove a recurrent tumour. When it comes to the survival rate and the identification of prognostic factors, a relationship between patient’s survival and microvascular invasion was observed. No statically significant relationship was established between the survival rate and the serologic levels of bilirubins and alpha-fetoprotein or the level of hepatocellular dysfunction, size or number of tumours. However, a more significant incidence of tumour recurrence was observed in patients with microvascular invasion in the histopathologic study. CONCLUSION: In spite of the reduced number of cases studied, the surgical treatment of the hepatocellular carcinoma produced bad results. A careful selection of cases where surgery could be an option may be a decisive factor to improve such results. Acareful selection of cases might be a decisive factor in order to improve such results.

RACIONAL: O estado de ativação imune provocado pelo vírus da hepatite C pode agir deleteriamente em indivíduos portadores do vírus da imunodeficiência humana, favorecendo a destruição mais rápida dos linfócitos CD4. Por outro lado, a recuperação imune observada após o início da terapia antiretroviral pode ser parcialmente embotada em indivíduos co-infectados pelo vírus da hepatite C. OBJETIVO: Avaliar o impacto da co-infecção pelo vírus da hepatite C na imunidade celular dos pacientes infectados pelo vírus da imunodeficiência humana. MÉTODOS: Foram avaliados pacientes co-infectados por ambos os vírus, atendidos prospectivamente no Ambulatório de Gastroenterologia do Hospital Nossa Senhora da Conceição, Porto Alegre, RS (grupo 1 - 385 pacientes), e monoinfectados pelo vírus da imunodeficiência humana cujos dados foram obtidos através da revisão dos prontuários do Serviço de Infectologia do mesmo Hospital (grupo 2 - 198 pacientes). Foram avaliados dados demográficos (gênero, raça, idade), contagem de células CD4 e CD8, relação CD4/CD8 e carga viral do vírus da imunodeficiência humana. O nível de significância adotado foi de 5%. RESULTADOS: Não houve diferença estatisticamente significativa quando avaliados os valores médios da contagem de células CD4 (374,7 ± 215,7 x 357,5 ± 266,0), CD8 (1.512,4 ± 7.274,6 x 986,7 ± 436,4) e da carga viral do vírus da imunodeficiência humana (83.744,2 ± 190.292,0 x 104.464,0 ± 486.880,5), respectivamente nos grupos 1 e 2, bem como na proporção de pacientes com relação CD4/CD8 menor que 1. CONCLUSÃO: A co-infecção por estes vírus não trouxe impacto negativo relevante em relação aos monoinfectados pelo vírus da imunodeficiência humana e as características de imunidade foram semelhantes.BACKGROUND: The immune activation provoked by the hepatitis C virus can be deleterious in patients with human immunodeficiency virus, favouring the destruction of CD4 cells. By the other side, the immune restoration observed after the onset of antiretroviral therapy can be partially obscured in patients with the hepatitis C virus. AIM: The objective of the present study was to evaluate the impact of coinfection by hepatitis C virus and the human immunodeficiency virus in the cellular immunity. METHODS: Two groups of patients were considered: coinfected patients were prospectively evaluated in the gastroenterology clinic at "Hospital Nossa Senhora da Conceição", Porto Alegre, RS, Brazil (group 1 - 385 patients), and monoinfected patients by human immunodeficiency virus based on the review of the charts from the infectious diseases clinic (group 2 - 198 patients). Demographic (gender, race, age) CD4 and CD8 cell count, CD4/CD8 index and human immunodeficiency virus viral load were evaluated. A 5% significance level was adopted. RESULTS: There were no difference between the parameters evaluated: mean CD4 count (374,7 ± 215,7 x 357,5 ± 266,0), CD8 (1.512,4 ± 7.274,6 x 986,7 ± 436,4) and HIV viral load (83.744,2 ± 190.292,0 x 104.464,0 ± 486.880,5) respectively in both groups evaluated, as well as the proportion of patients with CD4/CD8 rate below 1. CONCLUSION: Coinfection by both viruses did not have a negative impact in relation to monoinfection by human immunodeficiency virus, and the immune profile was similar in all groups.

BACKGROUND: The prevalence and consequences of occult HBV infection in patients with chronic liver disease by HCV remain unknown. AIMS: To evaluate the prevalence of occult HBV infection in a population of HCV-infected patients with hepatocellular carcinoma. METHODS: The serum samples were tested for HBV DNA by nested PCR and liver tissue analysis was carried out using the immunohistochemical technique of 66 HBsAg-negative patients: 26 patients with chronic hepatitis by HCV (group 1), 20 with hepatocellular carcinoma related to chronic infection by HCV (group 2) and 20 with negative viral markers for hepatitis B and C (control group). RESULTS: Occult HBV infection was diagnosed in the liver tissue of 9/46 (19.5%) HCV-infected patients. Prevalence of occult B infection was evaluated in the HCV-infected patients with and without hepatocellular carcinoma, and there were seven (77.7%) of whom from group 2, conferring a 35% prevalence of this group. No serum sample was positive for HBV DNA in the three groups. CONCLUSION: Occult infection B is frequently detected in liver tissue of HCV-infected patients, especially in cases of hepatocellular carcinoma. However large studies are needed to confirm that co-infection could determine a worse progress of chronic liver disease in this population.RACIONAL: A prevalência e as conseqüências da infecção oculta pelo VHB em pacientes com infecção crônica pelo VHC permanecem desconhecidas. OBJETIVO: Avaliar a prevalência da infecção oculta pelo VHB em uma população de pacientes infectados com o VHC e carcinoma hepatocelular. MÉTODOS: Amostras de soro foram testadas para o DNA do VHB por "nested" PCR e análise do tecido hepático utilizando imunoistoquímica de 66 pacientes HBsAg negativos: 26 pacientes com hepatite crônica pelo VHC (grupo 1), 20 com carcinoma hepatocelular relacionado ao VHC (grupo 2) e 20 com marcadores negativos para os vírus das hepatites B e C (grupo controle). RESULTADOS: Infecção oculta pelo VHB foi diagnosticada no tecido hepático de 9/46 (19.5%) pacientes com infecção pelo VHC. A prevalência foi avaliada nos pacientes com VHC com e sem carcinoma hepatocelular, estando presente em sete (77.7%) deste último grupo, conferindo 35% de infecção oculta pelo VHB nos pacientes com carcinoma hepatocelular. Nenhuma amostra de soro foi positiva para o DNA-VHB nos três grupos. CONCLUSÃO: A infecção oculta B é freqüentemente detectada no tecido hepático de pacientes infectados com VHC, especialmente nos casos de carcinoma hepatocelular. Entretanto, outros estudos com maior número de pacientes são necessários para confirmar se a co-infecção determina a progressão da doença hepática nesta população.

RACIONAL: Esteatose hepática é achado comum na hepatite pelo vírus C (VHC), principalmente nos pacientes com genótipo 3, podendo estar relacionada à resposta ao tratamento antiviral e prognóstico da hepatite crônica OBJETIVO: Determinar a presença de esteatose e de esteatohepatite não-alcoólica na hepatite crônica pelo VHC, correlacionando-as com o genótipo do VHC e com o grau de fibrose hepática. PACIENTES E MÉTODOS: Foram avaliados retrospectivamente 120 pacientes com hepatite crônica pelo VHC. A genotipagem foi avaliada em 102 pacientes. Todos os espécimes de biopsia hepática foram submetidos as colorações: picrosirius, hematoxilina-eosina e perls. O estádio da hepatite C foi realizado de acordo com a Classificação Brasileira e o diagnóstico de esteatohepatite não-alcoólica estabelecido de acordo com os critérios da American Association for the Study of Liver Diseases. O nível de significância considerado na analise estatística foi de 5% RESULTADOS: A esteatose foi encontrada em 65 dos 120 pacientes (54,2%), sendo leve em 37/65 (56,9%), moderada em 12/65 (18,5%) e intensa em 10/65 (15,4%). Quanto à fibrose, 80 de 120 pacientes (66,6%) tinham fibrose entre F0 e F2, e 40 (33,3%) tinham fibrose F3 ou F4. Esteatose foi mais freqüente no genótipo 3 (76,7%) em relação aos demais genótipos (49,0%). Não houve diferença na freqüência de esteatose quando comparados os pacientes com F3/F4 (52,5%) e demais graus de fibrose (54,4%). Esteatohepatite não-alcoólica foi diagnosticada em 8/120 casos (6,7%), sendo significativamente correlacionada com o genótipo 3 e com fibrose avançada (F3/F4) CONCLUSÕES: A presença de esteatose, assim como de esteatohepatite não-alcoólica na hepatite C, estão relacionados ao genótipo 3, sendo a esteatohepatite não-alcoólica correlacionada a graus mais avançados de fibrose.BACKGROUD: Hepatic steatosis is a common finding in patients with hepatitis C, mainly virus C genotype 3. Steatosis in these cases might be associated with antiviral treatment response and with prognosis of chronic hepatitis. AIMS: To determine the presence of steatosis and non-alcoholic steatohepatitis in chronic hepatitis C and its correlation with genotype and hepatic fibrosis. PATIENTS AND METHODS: One hundred and twenty patients with chronic hepatitis C were retrospectively evaluated; genotype was done in 102 patients. All specimens were stained with hematoxylin-eosin, picrosirius and perls. Staging of hepatitis C was scored by Brazilian Classification and the diagnosis of non-alcoholic steatohepatitis by the American Association for the Study of Liver Diseases criteria RESULTS: Steatosis was found in 65 of 120 cases (54.2%); it was mild in 37/65 (56.9%), moderate in 12/65 (18.5%) and severe in 10/65 (15.4%). In relation to fibrosis, 80 of 120 patients had mild fibrosis F0-F2 (66.6%) and 40 (33.3%) had more advanced fibrosis (F3 or F4). Steatosis was associated with genotype 3 (76.7%) in comparison with other genotypes (49,0%). There were no relationship between steatosis and advanced fibrosis F3/F4 (52,5%) or mild fibrosis (54,4%). Non-alcoholic steatohepatitis was diagnosed in 8/120 cases (6.7%) and was significantly associated with hepatitis C virus genotype 3 and with advanced fibrosis (F3 and F4) CONCLUSIONS: The presence of steatosis and non-alcoholic steatohepatitis in chronic hepatitis C are associated to genotype 3; moreover non-alcoholic steatohepatitis was correlated with more advanced fibrosis.

BACKGROUND: Nonalcoholic steatohepatitis is a chronic liver disease with a high prevalence in the general population and a potential to evolve into cirrhosis. It is speculated that iron overload could be associated with liver injury and unfavorable progress in affected patients. AIMS: To evaluate the prevalence of mutation of the hemochromatosis gene (HFE) in patients with nonalcoholic steatohepatitis and to correlate it with histological findings in liver specimens. PATIENTS AND METHODS: Twenty-nine patients with nonalcoholic steatohepatitis were evaluated. The presence of mutation in the hemochromatosis gene (C282Y and H63D) was tested in all patients and its result was evaluated in relation to hepatic inflammatory activity, presence of fibrosis, and iron overload in the liver. The control group was composed of 20 patients with normal liver function tests and 20 patients infected with the hepatitis C virus, with elevated serum levels of aminotransferases and with chronic hepatitis as shown by biopsy. RESULTS: Mutation of the hemochromatosis gene (C282Y and/or H63D) was diagnosed in 16 (55.2%) patients with nonalcoholic steatohepatitis, in 12 (60%) patients with hepatitis C and in 8 (40%) patients with no liver disease. No association was found between the presence of mutation and inflammatory activity, nor with the presence of fibrosis in patients with nonalcoholic steatohepatitis. An association was found between the presence of mutation and the occurrence of iron overload in liver, but there was no association between liver iron and the occurrence of fibrosis. CONCLUSIONS: The findings suggest that iron does not play a major role in the pathogenesis and progression of nonalcoholic steatohepatitis, and routine tests of the hemochromatosis gene mutation in these patients should not be recommended.RACIONAL: A esteatohepatite não-alcoólica é uma doença crônica, com elevada prevalência na população e com potencial evolutivo. Especula-se que a sobrecarga de ferro possa estar associada com a injúria hepática e com uma evolução desfavorável destes pacientes. OBJETIVOS: Avaliar a prevalência da mutação do gene da hemocromatose (HFE) em pacientes com esteatohepatite não-alcoólica e correlacioná-la com os achados histológicos hepáticos. PACIENTES E MÉTODOS: Foram avaliados 29 pacientes com esteatohepatite não-alcoólica. A presença da mutação do HFE (C282Y e H63D) foi testada em todos os pacientes e seu resultado foi avaliado em relação a atividade inflamatória hepática, presença de fibrose e depósitos hepático de ferro. Como grupo controle estudou-se 20 pacientes com provas de função hepática normal e 20 pacientes portadores do vírus da hepatite C, com elevação dos níveis de aminotransferases e biópsia revelando hepatite crônica. RESULTADOS: A mutação do HFE (C282Y e/ou H63D) foi diagnosticada em 16 (55,2%) pacientes com esteatohepatite não-alcoólica, em 12 (60%) pacientes com hepatite C e em 8 (40%) pacientes sem doença hepática. Não se observou associação entre a presença da mutação e a atividade inflamatória e a presença de fibrose nos pacientes com esteatohepatite não-alcoólica. Foi observada associação entre a presença de mutação e a ocorrência de depósitos de ferro hepático, porém, não ocorreu associação entre o ferro hepático e a ocorrência de fibrose. CONCLUSÕES: Os achados sugerem que o ferro não exerce papel importante na patogenia e na evolução da esteatohepatite não-alcoólica e a pesquisa rotineira da mutação do HFE nestes pacientes não deve ser recomendada.

RACIONAL: Os vírus das hepatites B (VHB) e C (VHC) e da imunodeficiência humana (HIV) utilizam a mesma rota de transmissão, sendo a prevalência de VHB e VHC em pacientes infectados pelo HIV maior do que aquela encontrada na população em geral. OBJETIVO: Determinar a prevalência de marcadores para hepatites B e C em uma população de pacientes com HIV, bem como os fatores de risco envolvidos. PACIENTES E MÉTODOS: Dentre os 5 870 prontuários de pacientes com HIV em acompanhamento no Serviço de Infectologia do Hospital Nossa Senhora da Conceição, Porto Alegre, RS, foram aleatoriamente selecionados 587 prontuários. Destes, foram considerados para análise retrospectiva aqueles em que havia sido pesquisado algum marcador para hepatites B (HBsAg, anti-HBc ou anti-HBs) ou C (anti-VHC), perfazendo o total de 343 pacientes. RESULTADOS: O HBsAg foi positivo em 14 de 306 (4,6%) pacientes, anticorpo anti-HBs, em 40 de 154 (26,0%) pacientes, e anti-HBc em 79 de 205 (38,5%) pacientes. Dentre aqueles que realizaram anti-VHC, 126 de 330 (38,2%) tinham-no positivo. Co-infecção por vírus B e C foi observada em 7 dentre os 296 pacientes que realizaram tanto o HBsAg, quanto o anti-VHC (2,4%). Dentre aqueles HBsAg positivos, a principal categoria de exposição foi o relacionamento homossexual masculino (50,0%). Dentre aqueles anti-VHC positivos, a principal categoria de exposição foi o uso de drogas ilícitas injetáveis (75,3%). Naqueles monoinfectados com HIV (185 pacientes), o fator de risco mais prevalente foi relacionamento heterossexual promíscuo ou com cônjuge infectado por HIV em 83 pacientes (44,9%). CONCLUSÃO: Em nosso meio, as co-infecções VHB-HIV e VHC-HIV são freqüentes, sendo observado maior impacto na associação do VHC com o HIV.BACKGROUND: Hepatitis B and C viruses and human immunodeficiency virus share the same route of transmission, and the prevalence of HBV and HCV infection in patients infected with HIV is greater than it is in the general population. AIM: To determine the prevalence of hepatitis B and C markers in a population of patients with HIV as well as the risk factors involved. PATIENTS AND METHODS: From 5,870 registration forms of patients with HIV of an Infectology Unit, 587 were randomly selected. From these, the 343 which had investigated the presence of any hepatitis B (HBsAg, anti-HBc or anti-HBs) or C (anti-HCV) marker were retrospectively analyzed. RESULTS: HBsAg was positive in 14/306 (4.6%), anti-HBs was positive in 40/154(26.0%), and anti-HBc in 79/205 (38.5%). The anti-HCV test was reactive in 126/330 (38.2%). HBV and HCV co-infection was observed in 7 of the 296 patients who had both HBsAg and anti-HCV tests (2.4%). For those who were HBsAg positive, the main exposure factor was homosexual intercourse (50.0%). For those who were anti-HCV reactive, the main risk factor was intravenous drug use (75.3%). In the HIV mono-infected (185 patients), the most prevalent exposure risk factor was promiscuous heterosexual practices or sexual intercourse with a spouse infected with HIV (83 patients - 44.9%). CONCLUSION: In our environment HBV-HIV and HCV-HIV co-infections are frequent, a greater relevance being observed in the association between HCV and HIV.

BACKGROUND: The prognosis of patients with chronic liver disease and spontaneous bacterial peritonitis is poor, being of great importance its prevention. AIM: To compare the effectiveness of trimethoprim-sulfamethoxazole versus norfloxacin for prevention of spontaneous bacterial peritonitis in patients with cirrhosis and ascites. PATIENTS AND METHODS: Fifty seven patients with cirrhosis and ascites were evaluated between March 1999 and March 2001. All of them had a previous episode of spontaneous bacterial peritonitis or had ascitic fluid protein concentration 2.5 mg/dL. The patients were randomly assigned to receive either 800/160 mg/day of trimethoprim-sulfamethoxazole 5 days a week or 400 mg of norfloxacin daily. The mean time of observation was 163 days for the norfloxacin group and 182 days for the trimethoprim-sulfamethoxazole group. In the statistical analysis, differences were considered significant at the level of 0.05. RESULTS: According to the inclusion criteria, 32 patients (56%) were treated with norfloxacin and 25 (44%) with trimethoprim-sulfamethoxazole. Spontaneous bacterial peritonitis occurred in three patients receiving norfloxacin (9.4%) and in four patients receiving trimethoprim-sulfamethoxazole (16.0%). Extraperitoneal infections occurred in 10 patients receiving norfloxacin (31.3%) and in 6 patients receiving trimethoprim-sulfamethoxazole (24.0%). Death occurred in seven patients (21.9%) who received norfloxacin and in five (20.0%) who received trimethoprim-sulfamethoxazole. Side effects occurred only in the trimethoprim-sulfamethoxazole group. CONCLUSION: In spite of the reduced number of patients and time of observation, trimethoprim-sulfamethoxazole and norfloxacin were equally effective in spontaneous bacterial peritonitis prophylaxis, suggesting that trimethoprim-sulfamethoxazole is a valid alternative to norfloxacin.RACIONAL: Devido ao prognóstico sombrio que a peritonite bacteriana espontânea acarreta aos pacientes com doença crônica parenquimatosa de fígado, a prevenção desta condição é fundamental. OBJETIVO: Comparar a eficácia da sulfametoxazol/trimetoprima versus norfloxacino para a prevenção de peritonite bacteriana espontânea em pacientes com cirrose e ascite. PACIENTES E MÉTODOS: Cinqüenta e sete pacientes com cirrose e ascite foram avaliados entre março de 1999 e março de 2001. Todos haviam apresentado um episódio prévio de peritonite bacteriana espontânea ou tinham proteína do líquido de ascite 2,5 mg dL. Os pacientes foram randomizados para receber sulfametoxazol/trimetoprima 800/160 mg por dia, 5 dias por semana, ou norfloxacino 400 mg diariamente. O período médio de acompanhamento foi de 163 dias para o grupo norfloxacino, 182 dias para o grupo sulfametoxazol/trimetoprima. Na análise estatística foi considerado um nível de significância de 5%. RESULTADOS: De acordo com os critérios de inclusão, 32 pacientes (56%) foram tratados com o norfloxacino e 25 (44%) com a sulfametoxazol/trimetoprima. A peritonite bacteriana espontânea ocorreu em três pacientes tratados com o norfloxacino (9,4%), comparado com quatro tratados com a sulfametoxazol/trimetoprima (16%). Infecções extra-peritoniais ocorreram em 10 pacientes recebendo o norfloxacino (31,3%) e em 6 recebendo a sulfametoxazol/trimetoprima (24,0%). Ocorreram sete óbitos entre os pacientes que receberam o norfloxacino (21,9%) e cinco entre os que receberam a sulfametoxazol/trimetoprima (20,0%). No que tange aos efeitos colaterais das medicações, estes só foram observados no grupo da sulfametoxazol/trimetoprima. CONCLUSÃO: A despeito do número de pacientes e do tempo de acompanhamento, a sulfametoxazol/trimetoprima e o norfloxacino foram igualmente efetivas na profilaxia da peritonite bacteriana espontânea, sugerindo que a primeira seja uma opção viável.

RACIONAL: A medida do gradiente de pressão venosa hepática é o método mais utilizado para a avaliação da pressão portal. Mais recentemente, a contagem de plaquetas no sangue tem sido apontada como um marcador não-invasivo da presença de hipertensão portal. OBJETIVO: Correlacionar a contagem de plaquetas com os valores do gradiente de pressão venosa hepática em uma população de pacientes cirróticos. PACIENTES E MÉTODOS: Foram estudados 83 pacientes com hepatopatia crônica que realizaram estudo hemodinâmico hepático, em período de 6 anos. Os pacientes foram divididos em grupos conforme a classificação de Child-Pugh e todos realizaram endoscopia digestiva alta para constatar a presença de varizes de esôfago, assim como tiveram a contagem sérica de plaquetas determinada. RESULTADOS: O número de plaquetas variou entre 45.000/mm³ e 389.000/mm³, com média 104.099 e desvio-padrão 58.776. O gradiente de pressão venosa apresentou média igual a 15,2 mm Hg e desvio-padrão igual a 6,4 mm Hg, variando de 1 a 29 mm Hg. Realizou-se regressão linear simples para verificar a correlação entre o gradiente de pressão venosa e o número de plaquetas, o que permitiu constatar fraca correlação entre ambos. Embora se tenha observado menor número de plaquetas, à medida que o calibre das varizes aumentava e nos pacientes com maior grau de disfunção hepatocelular - medida pela classificação de Child-Pugh - não se encontrou significância estatística. CONCLUSÃO: A despeito de não haver demonstrado correlação estatística entre o número de plaquetas com o gradiente de pressão venosa hepática e o grau de disfunção hepatocelular, pelas tendências observadas, acredita-se que ambos os fatores podem estar implicados na patogenia da plaquetopenia em pacientes cirróticos.BACKGROUND: Determination of hepatic venous pressure gradient is the main method used to assess portal pressure. Recently, platelet blood levels has been indicated as a non-invasive marker of the presence of portal hypertension. AIM: To correlate platelet blood levels with the hepatic venous pressure gradient among patients with cirrhosis. PATIENTS AND METHODS: A total of 83 cirrhotic patients who had undergone hepatic venous pressure gradient over the last 6 years were included. Patients were divided in groups according to Child-Pugh classification. All had upper digestive endoscopy to assess the presence of esophageal varices and platelet serum levels were recorded. RESULTS: Platelet serum levels range varied between 45,000/mm³ and 389,000/mm³ (mean: 104,099; standard deviation: 58,776). Mean hepatic venous pressure gradient was 15.2 mm Hg with a standard deviation of 6.4 mm Hg (range: 1 to 29 mm Hg). Simple linear regression analysis was applied to verify an association of hepatic venous pressure gradient and platelet serum levels, revealing a weak correlation between both variables. We observed a progressive reduction of serum platelet levels as esophageal varices diameter increased and hepatocellular function (established by Child-Pugh classification) decreased. However, these findings did not reach statistical significance. CONCLUSION: Despite the lack of a statistical significant correlation among serum platelet levels and hepatic venous pressure gradient or hepatocellular function, there was a clear tendency indicating that those variables could be involved in the pathogenesis of low platelet levels.

BACKGROUND: Considering the immunosuppression of patients with chronic liver disease, their response to vaccination is discussed in literature. AIMS: To evaluate the response of hepatitis B vaccine in patients with chronic hepatitis C virus infection. METHODS: This is a prospective study in which 85 patients with chronic hepatitis C virus infection (46.8 ± 9.4 years, 44.7% males) and 46 healthy adults (36.7 ± 11.1 years; 39.1% males) were evaluated. Confirmation of hepatitis C virus was obtained by the technique of polymerase chain reaction. Viral load was determined by the branched DNA method in 74 patients, and genotype was determined by sequencing in 73 patients. All patients and healthy adults received three doses of Engerix B® vaccine IM (at 0, 30 and 180 days). Serological responses to the vaccine were divided into three categories: seroprotection, when anti-HBs was >100 mUI/mL; seroconversion, when anti-HBs was 10-99 mUI/mL, and non-reagent, when anti-HBs was RACIONAL: Considerando a imunossupressão dos pacientes com doença hepática crônica, sua resposta à vacinação é discutida na literatura. OBJETIVOS: Avaliar a resposta à vacina anti-hepatite B em pacientes com hepatite crônica pelo vírus C. MÉTODOS: Estudo prospectivo avaliando 85 pacientes com infecção pelo vírus C (46,8 ± 9,4 anos, 44,7% homens) e 46 adultos saudáveis (36,7 ± 11,1 anos, 39,1% homens). Carga viral foi determinada através do b-DNA em 74 pacientes e o genótipo foi determinado por seqüenciamento em 73 pacientes. Todos os pacientes e os adultos saudáveis receberam três doses da vacina Engerix B® IM (aos 0, 30 e 180 dias). Resposta sorológica à vacina foi dividida em três categorias: soroproteção, quando anti-HBs era >"100 mUI/mL; soroconversão, quando anti-HBs era 10-99 mUI/mL e não-reagente, quando anti-HBs era

BACKGROUND: There still are controversies concerning the vertical transmission of hepatitis C virus. AIM: To evaluate the prevalence of antibodies against hepatitis C virus in pregnant women, as well as the rate of vertical transmission of this virus. PATIENTS AND METHODS: Between August 1998 and November 1999, 1,090 consecutive pregnant women were screened for anti-hepatitis C virus; positive results were confirmed by the polymerase chain reaction assay. Patient's viral load was evaluated by the branched deoxyribonucleic acid assay. Hepatitis C virus genotype was identified by direct sequencing of the polymerase chain reaction amplification products. The same tests were performed in the children born from infected mothers at the 1st and 6th month of life. RESULTS: Of the 1,090 mothers surveyed, 29 were positive for anti-hepatitis C virus (prevalence of 2.66%). Twenty-five patients presented with hepatitis C virus RNA, with a median hepatitis C virus viral load of 3.132 ± 5.891 MEq/mL. Twenty-two patients (six human immunodeficiency virus-coinfected) were followed and gave birth to 23 children; 18 of them had blood samples tested at the 1st month of life, and 22, at the 6th month. Vertical transmission rate was 5.56%; it affected a girl who had hepatitis C virus RNA detectable only in the 1st month sample (41.570 MEq/mL). The mother who transmitted hepatitis C virus was coinfected with human immunodeficiency virus and presented with an hepatitis C virus viral load of 3.765 MEq/mL, with 100% homology with her daughter's hepatitis C virus genotype. CONCLUSION: These results suggest that the prevalence of hepatitis C virus infection in pregnant women should not be neglected, and early diagnosis of vertical transmission and the follow up of infected children should be emphasized.RACIONAL: Ainda existem controvérsias em relação à transmissão vertical do vírus da hepatite C (VHC). OBJETIVO: Avaliar a prevalência dos anticorpos contra o VHC (anti-VHC) em mulheres grávidas, bem como a percentagem de transmissão vertical observada. PACIENTES E MÉTODOS: Entre agosto de 1998 e novembro de 1999, 1.090 mulheres grávidas consecutivas realizaram a determinação do anti-VHC. A confirmação do teste foi feita pela reação em cadeia da polimerase. A carga viral foi determinada pelo b-DNA e o genótipo por seqüenciamento. Os mesmos testes foram realizados no 1º e 6º mês de vida, nas crianças nascidas de mães infectadas. RESULTADOS: Das 1.090 mães estudadas, 29 apresentaram positividade para o anti-VHC (prevalência de 2,66%). Em 25 pacientes foi demonstrado o RNA do VHC, sendo que a carga viral média foi de 3,132 ± 5,891 MEq/mL. Vinte e duas pacientes (6 co-infectadas com o vírus da imunodeficiência humana) foram seguidas e deram à luz a 23 crianças, das quais 18 tiveram seu sangue testado no 1º mês e 22 no 6º mês. Foi observada transmissão vertical em 5,56% dos casos. Assim, em uma criança do sexo feminino foi detectado o RNA do VHC (41,570 MEq/mL). A mãe desta criança estava co-infectada pelo vírus da imunodeficiência humana e apresentava carga viral de 3,765 MEq/mL, com 100% de homologia no genótipo viral. CONCLUSÃO: Estes resultados sugerem que a prevalência da infecção pelo VHC em gestantes não deve ser negligenciada e que um diagnóstico precoce e o seguimento das crianças infectadas deve ser preconizado.

RACIONAL: A infecção crônica pelo vírus da hepatite C é importante problema de saúde pública. OBJETIVOS: Analisar os resultados do tratamento combinado interferon-alfa/ribavirina e identificar fatores preditivos de resposta em pacientes adultos com hepatite crônica C de um programa público de fornecimento de medicamentos. PACIENTES E MÉTODOS: Estudo retrospectivo de registros consecutivos de 400 pacientes com hepatite crônica C tratados com interferon/ribavirina em programa estabelecido pela Secretaria Estadual de Saúde do Rio Grande do Sul, Porto Alegre, RS, no período de 1999 a 2000. RESULTADOS: A distribuição entre homens e mulheres foi similar, e a média de idade foi de 46,5 ± 10,3 anos. Observou-se resposta ao final do tratamento e resposta sustentada em 49% e 32% dos pacientes, respectivamente. Resposta sustentada foi significativamente maior nas mulheres e em pacientes infectados com genótipos não-1, não se tendo observado diferença quando avaliada a idade e o grau de atividade e estágio histológico. CONCLUSÃO: Em pacientes adultos com hepatite crônica C, a resposta ao tratamento combinado interferon-alfa/ribavirina foi observada em um terço deles. Taxas maiores de resposta foram observadas em mulheres e em pacientes infectados com genótipos não-1.BACKGROUND: Chronic infection by hepatitis C virus is an important public health issue. AIMS: To assess the effectiveness of a combination therapy with interferon-alpha plus ribavirin and to identify predictive factors of response in adult patients with chronic hepatitis C in a public drug supply program. PATIENTS AND METHODS: A retrospective study of consecutive records of 400 patients with chronic hepatitis C treated with interferon-a plus ribavirin therapy, as part of a health program conducted by the Department of Health of the State of Rio Grande do Sul, Porto Alegre, RS, southern Brazil, between 1999 and 2000, was carried out. RESULTS: Sex distribution was similar, and the average age was 46.5 ± 10.3 years. Response at the end of the treatment was observed in 49% of patients, and sustained response was observed in 32% of them. Sustained response was significantly higher in females and in patients infected by genotypes other than 1. We did not observe significant differences in terms of age or histological stage and activity score. CONCLUSION: In adult patients with chronic hepatitis C, combination therapy with interferon-alpha plus ribavirin was effective in one third of patients. Higher rates of response were observed in women and in patients infected by genotypes other than 1.

BACKGROUND: Endoscopic procedures can develop bacteremia. Patients with chronic liver disease are more predisposed to undergo bacteremia and infections because they are immunocompromised. AIMS: The purpose of this study was to determine the incidence of bacteremia in cirrhotics submitted to endoscopic variceal ligation. METHODS: Three groups of 40 patients each were studied. One group was made up of patients with cirrhosis who were submitted to ligation, a second group was composed of cirrhotics who underwent esophagogastroduodenoscopy only, and a third group was composed of patients without liver disease who underwent esophagogastroduodenoscopy. Blood was sampled from all patients for culture, both in aerobic and in anaerobic mediums, immediately before endoscopy and at 5 and 30 minutes after its completion. RESULTS: Blood culture was positive in 6 samples. In 4 of these, the bacteria (Staphylococcus hominis hominis, Staphylococcus auricularis, Acinetobacter lwoffii, and coagulase-negative staphylococcus) were isolated before the endoscopic procedure and thus were considered as contamination. In the ligation group, a streptococcus of the viridans group was isolated 5 minutes after the procedure, and in the cirrhosis without ligation group, a Staphylococcus epidermidis was isolated at 30 minutes. None of the patients showed clinical evidence of infection. CONCLUSIONS: The bacteremia incidence in cirrhotic patients submitted to variceal ligation was 2.5%, showing no difference from the control groups.

BACKGROUND/AIMS: Spontaneous bacterial peritonitis (SBP) is an important complication in cirrhotic patients. The aim of the present study was to assess the incidence, predictive factors and prognosis for renal impairment (RI) after SBP in cirrhotic patients from southern Brazil.

RACIONAL: A peritonite bacteriana espontânea é complicação freqüente nos pacientes com cirrose e ascite, apresentando taxa de recurrência em 1 ano próxima de 70%. OBJETIVOS: Avaliar a prevalência da peritonite bacteriana espontânea em pacientes com ascite por hepatopatia crônica e o impacto da sua presença na sobrevida dos mesmos. PACIENTES/MÉTODOS: Foram avaliadas 1030 internações de pacientes com cirrose e ascite, tendo sido documentados 114 episódios de peritonite bacteriana espontânea em 94 pacientes. Em todos foi realizada paracentese com análise do líquido ascítico. O diagnóstico desta complicação foi estabelecido quando o número de polimorfonucleares do líquido de ascite fosse superior a 250 células por mm³. RESULTADOS: A prevalência da peritonite bacteriana espontânea foi de 11,1% e sua mortalidade de 21,9%. A infecção foi adquirida na comunidade em 61,4% e no hospital em 37,7%, sendo as taxas de óbito de 18,6% e 27,9%, respectivamente. Houve controle da infecção, documentado pela análise do líquido de ascite coletado por paracentese realizada 48 horas após o início da antibioticoterapia, em 91,1% dos episódios. Nestes casos a mortalidade foi de 16,7%. Nos casos em que a infecção não foi controlada, o óbito ocorreu em 80,0%. Em 22,3% da amostra foi documentado o uso do antibiótico profilático sem, no entanto, demonstrar haver diferença significativa quanto à mortalidade, quando comparados aos pacientes que não realizaram profilaxia. CONCLUSÕES: A peritonite bacteriana espontânea é infecção freqüente nos pacientes com ascite por hepatopatia crônica, com prognóstico reservado, principalmente na ausência de resposta precoce à antibioticoterapia.

Racional - A esteatohepatite não-alcoólica e a doença hepática alcoólica apresentam similaridade histológica e em algumas situações, o diagnóstico diferencial das mesmas pode ser difícil, pois alguns pacientes não revelam o consumo abusivo de álcool. Objetivo- Avaliar a utilidade da determinação do índice AST/ALT no diagnóstico diferencial da esteatohepatite não-alcoólica e da doença hepática alcoólica. Pacientes e Métodos -Foram estudados 29 pacientes obesos com esteatohepatite não-alcoólica, cujo o diagnóstico foi realizado após exclusão de outras causas de doença hepática e que na biopsia apresentasse, no mínimo, esteatose macrovesicular associada a infiltrado inflamatório lobular e injúria hepatocelular. Como grupo controle, foram estudados 28 pacientes com doença hepática alcoólica. Resultados - Nos pacientes com esteatohepatite não-alcoólica, a média de AST foi de 52,3 ± 21,2 U/L e a de ALT de 90,1 ± 37,9 U/L, sendo o índice AST/ALT menor que 1 em todos os casos. No grupo controle, a média de AST foi de 140 ± 82,5 U/L e a de ALT foi de 50,6 ± 40,3 U/L. O índice AST/ALT foi superior a 1 em todos os pacientes e a 2 em 24 (85,7%), o que foi estatisticamente significativo quando comparado aos pacientes com esteatohepatite não-alcoólica. Conclusão- O índice AST/ALT parece ser útil no diagnóstico diferencial das hepatopatias, sendo que valores inferiores a 1 sugerem fortemente a hipótese de esteatohepatite não-alcoólica.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a major disorder in patients with persistent changes in aminotransferase activity who test negative for viral markers and autoantibodies. Although NASH has been correlated with obesity, no study has been carried out exclusively with nondiabetic obese patients.