Peginterferon plus ribavirin and sustained virological response rate in HCV-related advanced fibrosis: a real life study

Background: Tolerance and response to antiviral HCV treatment is poor in advanced fibrosis. The aim of this study was to assess SVR rate and its predictive factors in HCV advanced fibrosis patients treated in real life with full dose PEG-IFN plus RBV and to evaluate the adverse events related to treatment. Methods: A multicentric, retrospective study was conducted at six university hospitals. METAVIR F3 and F4 HCV monoinfected patients who were treated with PEG-IFN and RBV had their data analyzed. A stepwise logistic regression analysis was performed to identify the variables independently related to SVR. Adverse events were recorded during treatment. Results: 308 patients were included, 75% genotype 1 and 23% genotype 3. METAVIR F3 was present in 39% and F4 in 61% of patients. The median Child Pugh score for F4 patients was 5 (5–9). The global SVR rate was 34%, 11% were relapsers and 55% were nonresponders. SVR rates were similar between patients treated with PEG-IFN alfa 2a or alfa 2b (p = 0.24). SVR rates according to Child–Pugh score were 26% (Child A) and 18% (Child B). The independent factors related to SVR in F4 patients were genotype 3, RVR and fewer Child Pugh score points. Treatment interruption occurred in 31% patients and death occurred in 1.9%, all with liver cirrhosis. Conclusion: Treatment of HCV in patients with advanced fibrosis should not be postponed. However, a very careful evaluation of cirrhotic patients must be performed before treatment is indicated and careful monitoring is required during treatment. .

Encefalopatia hepática: relatório da 1ª reunião monotemática da Sociedade Brasileira de Hepatologia / Hepatic encephalopathy: report 1st monothematic meeting of the Brazilian Society

A encefalopatia hepática (EH) é um distúrbio funcional do sistema nervoso central (SNC) associado à insufi ciência hepática, de fisiopatologia multifatorial e complexa. Devido aos avanços no conhecimento sobre o manejo da EH na cirrose e na insuficiência hepática aguda (IHA), a diretoria da Sociedade Brasileira de Hepatologia (SBH) promoveu uma reunião monotemática acerca da fi siopatologia, diagnóstico e tratamento da EH, abordando aspectos controversos relacionados ao tema. Com a utilização de sistemática da medicina baseada em evidências, foram abordados o manejo da EH e da hipertensão intracraniana na IHA, o manejo da EH episódica na cirrose, as controvérsias no manejo da EH e a abordagem da EH mínima. O objetivo desta revisão é resumir os principais tópicos discutidos na reunião monotemática e apresentar recomendações sobre o manejo da síndrome votadas pelo painel de expertos da SBH.

Hepatic encephalopathy (HE) is a functional disorder of the central nervous system (CNS) associated with liver failure, either end-stage chronic liver disease or fulminant hepatic failure. Its pathogenesis remains complex and poorly understood. In view of recent advances in the management of HE, the Brazilian Society of Hepatology endorsed a monothematic meetingregarding HE in order to gather experts in the to discuss related data and to draw evidence-based recommendations concerning: management of HE and intracranial hypertension in FHF, treatment of episodic HE in cirrhosis, controversies in the management of EH including difficult to treat cases and diagnostic and treatment challenges for minimal HE. The purpose of this review is to summarize the lectures and recommendations made by the panel of experts of the Brazilian Society of Hepatology.

Osteodistrofia hepática / Hepatic osteodystrophy

Osteodistrofia hepática é distúrbio de mineralização óssea associada à doença hepática crônica, sendo a osteoporose, e mais raramente a osteomalácia, sua forma de apresentação clínica. Apesar de pouco diagnosticada e com prevalência de grande variação na literatura, na maioria das vezes, apresenta-se de forma assintomática e, quando não identificada, aumenta consideravelmente o risco de fratura e sequelas permanentes. Seu diagnóstico, portanto, requer alta suspeição e faz-se, na prática clínica, por meio da avaliação da densitometria óssea. De fisiopatogenia multifatorial, envolve fatores genético, ambiental e do próprio estado clínico-nutricional do paciente. Uma atenção maior deve ser despendida a hepatopatas desnutridos, com cirrose hepática avançada, doença colestática crônica e transplantados pelo maior risco de desmineralização óssea. Nesta revisão, será discorrido sobre o metabolismo fisiológico da síntese óssea e a fisiopatologia do distúrbio de mineralização óssea, desde mecanismos fisiopatogênicos na doença hepática crônica, seu diagnóstico e revisão da terapêutica atual empregada.

Hepatic osteodystrophy is a disorder of bone mineralization associated to liver disease, clinically manifested by osteoporosis and more rarely osteomalacia. Although seldomly diagnosed and varying greatly in literature, most of the time, it presents asymptomatically and, when it is not recognized, it enhances considerably the risk of fracture and permanent sequelae. Indeed it requires a high grade of suspicion and it is confirmed by means of bone densitometry evaluation in clinical practice. Presenting with a multifactorial physiopathology, it involves factors, such as genetical, environmental, and patient clinical-nutritional status. A greater attention must be spent on patients with liver disease, especially those malnourished, with advanced cirrhosis, chronic cholestatic disease, and transplanted, because of a higher risk of bone demineralization. In this data, it will be reviewed the bone synthesis metabolism and the physiopathology of bone mineralization disorder ? since fisiopatogenic mechanisms in chronic liver disease, diagnosis and recent therapeutic review employed.

Osteodistrofia hepática / Hepatic osteodystrophy

Osteodistrofia hepática é distúrbio de mineralização óssea associada à doença hepática crônica, sendo a osteoporose, e mais raramente, a osteomalácia, sua forma de apresentação clínica. Apesar de pouco diagnosticada e prevalência com grande variação na literatura, na maioria das vezes, apresenta-se de forma assintomática e, quando não identificada, aumenta consideravelmente o risco de fratura e sequelas permanentes. Seu diagnóstico, portanto, requer alta suspeição e faz-se, na prática clínica, por meio da avaliação da densitometria óssea. De fisiopatogenia multifatorial, envolve fatores genético, ambiental e do próprio estado clínico-nutricional do paciente. Uma atenção maior deve ser despendida a hepatopatas desnutridos, com cirrose hepática avançada, doença colestática crônica e transplantados pelo maior risco de desmineralização óssea. Nesta revisão, será discorrido sobre o metabolismo fisiológico da síntese óssea e a fisiopatologia do distúrbio de mineralização óssea, desde mecanismos fisiopatogênicos na doença hepática crônica, seu diagnóstico e revisão da terapêutica atual empregada.

Hepatic osteodystrophy is a disorder of bone mineralization associated to liver disease, clinically manifested by osteoporosis and more rarely osteomalacia. Although seldomly diagnosed and varying greatly in literature, most of the time, it presents asymptomatically and, when it is not recognized, it enhances considerably the risk of fracture and permanent sequelae. Indeed it requires a high grade of suspicion and it is confirmed by means of bone densitometry evaluation in clinical practice. Presenting with a multifactorial physiopathology, it involves factors, such as genetical, environmental, and patient clinical-nutritional status. A greater attention must be spent on patients with liver disease, especially those malnourished, with advanced cirrhosis, chronic cholestatic disease, and transplanted, because of a higher risk of bone demineralization. In this data, it will be reviewed the bone synthesis metabolism and the physiopathology of bone mineralization disorder - since fisiopatogenic mechanisms in chronic liver disease, diagnosis and recent therapeutic review employed.

Acute hepatotoxicity caused by enalapril: a case report.

A case of enalapril-induced acute hepatotoxicity with an unusual morphology is described. This morphology was characterized by macro- and microvesicular steatosis associated with neutrophil infiltration and Mallory bodies, occasionally with satellitosis. These alterations were most abundant in zone 1 of the periportal region, less common in zone 2 and rare in zone 3. There was also confluent periportal necrosis with sinusoidal fibrin deposits associated with intense ductal metaplasia and an infiltrate of inflammatory cells that included plasmocytes and a few eosinophils, as well as focal biliary damage. This morphology, that may be referred as "predominantly periportal steatohepatitis", was distinct from that associated with non-alcohol and alcohol-induced steatohepatitis, both initiated in acinar zone 3 and subsequently extended to other zones.

Microwave coagulation versus sclerotherapy after band ligation to prevent recurrence of high risk of bleeding esophageal varices in Child-Pugh's A and B patients.

BACKGROUND: The combination of endoscopic band ligation (EBL) with either endoscopic injection sclerotherapy (EIS) or thermal therapy has been shown to reduce recurrence of esophageal varices compared to EBL alone. The aim of this prospective trial was twofold: 1) to evaluate the safety and efficacy of EBL used in association with microwave coagulation (MC), a thermal endoscopic therapy method, for treating esophageal varices and preventing recurrence; and 2) to compare these results to the joint application of EBL and EIS. METHODS: Seventy cirrhotic patients with bleeding esophageal varices were treated with EBL until only thin vessels remained. Thirty-six randomly selected patients received EIS (group A) and 34 received MC (group B) until complete eradication had been achieved. Endoscopic follow-up was performed to detect recurrence. The effectiveness of the treatment was measured using variceal recurrence, rebleeding, intervention complications, and recurrence factors. RESULTS: During follow-up evaluations averaging 34.9 +/- 11.4 months, no significant differences were found between groups A and B in variceal recurrence (27.7 vs. 17.6%, P = 0.31) or rebleeding (8.3 vs. 0%, P = 0.23). Complications were rare, with no difference detected between groups. The presence of gastric varices influenced recurrence with an odds ratio of 3.9 (95% CI 1.14-13.1, P = 0.029). CONCLUSIONS: Application of MC to esophageal varices after band ligation is safe. The post-MC recurrence rate may be comparable to that observed following the combined treatment of EBL and EIS. The presence of gastric varices increases the risk of esophageal variceal recurrence.

High serum laminin and type IV collagen levels in schistosomiasis mansoni

RACIONAL: A fibrose hepática é caracterizada por um aumento progressivo na quantidade do tecido conjuntivo hepático, que é formado pelo aumento na deposição de componentes da matriz extracelular, tendo sido encontrada grande quantidade desses componentes no fígado de pacientes com esquistossomose mansoni. A laminina e o colágeno tipo IV têm sido investigados em várias doenças hepáticas, mas seu papel na esquistossomose ainda não está esclarecido. OBJETIVOS: Avaliar a fibrose hepática na esquistossomose mansoni através da determinação sérica de laminina e colágeno tipo IV, considerados marcadores séricos de fibrose hepática. PACIENTES E MÉTODOS: Foram incluídos 82 indivíduos, sendo 18 indivíduos normais, como controle e 64 pacientes com esquistossomose mansoni, em suas diferentes formas clínicas: intestinal (grupo I), hepatointestinal (grupo II), hepatoesplênica compensada (grupo III) e hepatoesplênica descompensada (grupo IV). Os níveis séricos de laminina e colágeno tipo IV foram determinados por método imunoenzimático sanduíche. RESULTADOS: Os valores médios de colágeno tipo IV e laminina estiveram significativamente aumentados em pacientes com esquistossomose, quando comparados com os controles. Em relação às formas clínicas, os níveis séricos de colágeno tipo IV estiveram significativamente aumentados nos grupos II e IV, em relação aos controles e entre as formas hepatoesplênica descompensada e intestinal. Os níveis séricos de laminina estiveram significativamente aumentados nos grupos II, III e IV e entre o grupo IV e II. Não foi encontrada correlação entre os valores médios de colágeno tipo IV e laminina com o grau de espessamento periportal, detectado por ultra-sonografia. Foi encontrada correlação positiva entre colágeno tipo IV e laminina nos grupos II e IV. CONCLUSÕES: Os resultados mostram que existe aumento de produção de colágeno tipo IV e laminina na esquistossomose mansoni, surgindo altos níveis desde as fases iniciais do envolvimento hepático da doença, até as formas mais avançadas, sugerindo ser um útil fator para detecção de progressão da doença.

Grading and staging chronic hepatitis C and its relation to genotypes and epidemiological factors in Brazilian blood donors.

Progression of chronic hepatitis C is known to be associated with some factors, but influence of HCV genotypes is still controversial. Association between HCV genotypes and other risk factors was examined to determine which factors are associated with progression of infection. One hundred consecutive anti-HCV positive volunteer blood donors were evaluated for several risk factors, examined for HCV genotypes, and submitted to hepatic biopsy and biochemical exams.HCV genotyping were carried out in 89 patients and hepatic biopsy in 78. Transmission routes were found to be illicit intravenous drug use (26%), Gluconergan use in a non-safe manner (48%) and blood transfusion (15%). HCV genotype was 1 in 45%, 3 in 40%, and it was not associated with the stage of fibrosis or with inflammatory activity. There was no significant association of factors related to infection, chronic alcohol use, or duration of illness, with progression of the lesion. There was a significant association of aminotransferase levels and the fibrosis stage. Univariate analysis showed that the age at contamination, patient's age, GT-gamma, and aminotransferase levels over three times the upper normal limits, were associated with fibrosis stages 2 to 4. Multivariate analysis detected age (odds ratio=1.19), and GT-gamma (odds ratio=2.02) as independent factors.

Grading and staging chronic hepatitis C and its relation to genotypes and epidemiological factors in brazilian blood donors

Progression of chronic hepatitis C is known to be associated with some factors, but influence of HCV genotypes is still controversial. Association between HCV genotypes and other risk factors was examined to determine which factors are associated with progression of infection. One hundred consecutive anti-HCV positive volunteer blood donors were evaluated for several risk factors, examined for HCV genotypes, and submitted to hepatic biopsy and biochemical exams.HCV genotyping were carried out in 89 patients and hepatic biopsy in 78. Transmission routes were found to be illicit intravenous drug use (26 percent), Gluconergan® use in a non-safe manner (48 percent) and blood transfusion (15 percent). HCV genotype was 1 in 45 percent, 3 in 40 percent, and it was not associated with the stage of fibrosis or with inflammatory activity. There was no significant association of factors related to infection, chronic alcohol use, or duration of illness, with progression of the lesion. There was a significant association of aminotransferase levels and the fibrosis stage. Univariate analysis showed that the age at contamination, patient's age, GT-gamma, and aminotransferase levels over three times the upper normal limits, were associated with fibrosis stages 2 to 4. Multivariate analysis detected age (odds ratio=1.19), and GT-gamma (odds ratio=2.02) as independent factors.

High serum laminin and type IV collagen levels in schistosomiasis mansoni.

BACKGROUND: Fibrosis is the process of excessive deposition of collagen and other extra cellular matrix components and large amounts of these components have been shown in periovular schistosomal granulomas, especially in the liver. Laminin and type IV collagen have been investigated in various hepatic disorders but their accuracy in fibrosis detection and in the evaluation of its progression in schistosomiasis have not been fully explained. AIM: To measure the serum levels of two markers of fibrosis, laminin and type IV collagen in schistosomiasis. PATIENTS AND METHODS: Sixty-four patients with different clinical forms of schistosomiasis mansoni: intestinal (group I), hepatointestinal (group II), compensated (group III) and decompensated hepatosplenic (group IV) and 18 healthy volunteers were included. RESULTS: Serum type IV collagen and laminin levels were significantly increased in patients compared to controls. At about clinical forms, serum type IV collagen was increased in groups II and IV, compared to controls and was significantly higher in group IV than in group I. Serum laminin was significantly increased in groups II, III and IV and was significantly higher in group IV than in group II. Serum type IV collagen was closely correlated with serum laminin in groups II and IV. CONCLUSIONS: Connective tissue marker levels did not correlate with periportal thickness. In schistosomiasis mansoni there is an increase of type IV collagen and laminin levels at the initial stage of the disease, as well as in advanced forms. We also suggest that these markers may be a useful predictor of disease progression.

Progression of liver fibrosis in blood donors infected with hepatitis C virus.

BACKGROUND/AIMS: Chronic hepatitis by HCV is progressive towards cirrhosis, with variable rate. We evaluated the rate of fibrosis progression (RFP), risk factors associated with advanced fibrosis (F3 and F4), and estimated the evolution time to cirrhosis. METHODS: We transversely selected 142 blood donors infected only with HCV, with a known route of infection, submitted to liver biopsy at admission. RFP= ratio between stage of fibrosis (METAVIR)/estimated duration of infection in years. Non-parametric tests and logistic regression analysis, with significance level of 5% were used. RESULTS: Median RFP was 0.086 U/year (0.05-0.142). Ten patients had F4 and 25 had F3. Median RFP values were significantly different (p=0.001) from one age group at contamination to the others and ALT and AST levels. There were no differences in the expected evolution to cirrhosis between intermediate fibrosers (F2) and the rapid fibrosers (F3 and F4). The independent variables associated with advanced fibrosis were ALT (OR 7.2) and GGT (OR 6.4) and age at inclusion (OR 1.12). CONCLUSION: This study suggests that RFP is extremely variable, it is exponential with age, and mainly influenced by host characteristics, especially age at contamination and possibly ethnical group. These asymptomatic patients had high percentage of fibrosis F2, F3 and F4.

Fine needle aspiration biopsy for improving the diagnostic accuracy of cut needle biopsy of focal liver lesions.

OBJECTIVE: To determine the value of fine needle aspiration biopsy (FNAB) in comparison to cut needle biopsy (CNB) for the diagnosis of malignancy of focal liver lesions. STUDY DESIGN: A retrospective analysis was conducted on 68 FNAB and 49 CNB procedures performed on 62 patients with focal liver lesions. RESULTS: Cytology permitted a diagnosis of the lesion in 78% of cases. When punctures with insufficient material were excluded (11), the diagnostic accuracy of FNAB was 93%. For the 49 patients who underwent both procedures, FNAB and CNB had the same diagnostic accuracy, 78%, when considered separately and of 88% when considered in combination. Sensitivity, specificity and positive predictive value were similar for the 2 techniques. The negative predictive value was 64% for FNAB and CNB used separately and reached 78% when the 2 techniques were combined. There were no complications during the execution of FNAB and CNB. CONCLUSION: FNAB is an effective and safe method for the diagnosis of focal hepatic lesions, with diagnostic accuracy similar to that of CNB. When the 2 techniques are combined, the accuracy of the diagnosis of malignancy of focal liver lesions increases.

Marcadores sorológicos das hepatites virais no transplante renal / Serological markers of viral hepatitis in kidney transplatation

Com o objetio de verificar a prevalência da infecçoes virais pelos viros B e C da hepatite, em pacientes que realizaram transplante renal no Hospital das clínicas da Unicamp, os autores estudaram 134 indivíduos (44 mulheres, 90 homens, média de idade: 31,3 ñ 9,89 anos). a prevalência de HBsAg encontrada foi de 12,2por cento. Apresentaram anti-HBc e antiHBs positivos 93 pacientes ( 68,4por cento), sugerindo ter tido infecção prévia pelo vírus, com provável clearance deste. Não houve associação entre alterações das aminotransferases e a presença deHBsAg no soro. apesar da análise de regressão logistica ter mostrado que nos individuos que utilizaram mais de seis unidades de sangue ou hemoderivados o risco de serem HBsAg positivos era duas vezes maior em relação àqueles que receberam um número menor de unidades (odds ratio=2), esse resultado não foi estatisticamente significante (p= 0,30). Com relação ao vírus C, a prevalência de anti-HCV sérico foi de 47,5por cento, não havendo associação entre a presença de infecção pelo vírus C e alteraçoes de ALT. O número de bolsas de sangue transfundidas teve associação levemente significante com o marcador desta infecção viral (p=0,06) quando o seu número foi superir a seis, bem como se observou que esse número acarreta aumento de risco de infecção de 2,1 vezes (p=0,06). O tempo de hemodialise teve diferença estatisticamente significante entre indidíduos infectados e não infectados, tanto para infecção pelos vírus B (p=0,0457) quanto pra a infecção pelo vírus C (p= 0,0019). Conclusão: a pevalência de infecção pelo vírus B e C é elevada em indivíduos submetidos ao TX renal no HC da Unicamp,, associando-se principalmente ao tempo de hemodialise pré-transplante, mostrando a necessidade de medidas rigorosas de combate à propagação por esses vírus nas unidades de hemodiálise. GED19(5):193-198,2000

TTV (TT vírus) - sua importância na patogenia da doença hepática: mito ou realidade? / TTV (TT virus) - Its relevance in the pathogenesis of liver disease: myth or reality?

O TTV é um vírus identificado inicialmente por Nishizawa e col. como agente associado à hepatite pós-transfusional não A-não G. As taxas de prevalência variam muito, de um país a outro, dados recentes mostrando níveis elevados de detecção de TTV DNA no soro de pacientes com hepatite crônica de etiologia desconhecida e, mesmo, de indivíduos normais. Os estudos realizados até o presente não sustentam a hipótese de que esse vírus esteja relacionado à paatogenia da doença hepática

Gelatin particle indirect agglutination test for serodiagnosis of schistosomiasis: comparative study with enzyme-linked immunosorbent assay

Um novo teste sorologico, o teste de aglutinacao com particulas de gelatina (TAPG), foi utilizado para o diagnostico sorologico de esquistossomose mansonica. Esta tecnica mostra que a sensibilidade (90,6 por cento) e especificidade (97,8 por cento) chegam proximas do teste de enzima imunoensaio. O TAPG pode ser facil e rapidamente realizado sem equipamentos especializados usando particulas liofilizadas sensibilizadas com o antigeno. O teste mostrou ser tambem util em condicoes de campo para triagem em massa da infeccao pelo Schistosoma mansoni.