Peritonite bacteriana espontânea na cirrose hepática: prevalência, fatores preditivos e prognóstico Spontaneous bacterial peritonitis in hepatic cirrhosis: prevalence, predictive factors and prognosis

OBJETIVO: Investigar prevalência, fatores preditivos e prognóstico dos episódios de Peritonite Bacteriana Espontânea (PBE) na cirrose hepática. METODOLOGIA: Estudamos, prospectivamente, 143 pacientes com cirrose hepática, ambulatoriais ou internados, que foram atendidos nos Serviços de Clínica Médica do HUCFF e de Gastroenterologia do HUPE no período de janeiro/95 a janeiro/96. Estes pacientes foram submetidos a questionário, exame físico, colheita de sangue e paracentese abdominal com colheita de líquido ascítico (LA) e, então, acompanhados por um período médio de 4 meses, onde a taxa de mortalidade foi determinada. RESULTADOS: A prevalência de PBE foi cerca de 20%, sendo 24% PBE cultura positiva, 66% Ascite Neutrofílica cultura negativa e 10% Bacterioascite. Na análise univariada, alcançaram significância estatística (p=0.05) como fatores preditivos do episódio de PBE: HGI na semana anterior; passado de encefalopatia hepática; classificação de Child; dosagens séricas de proteínas, albumina, C3, C4 e uréia; dosagens no LA de C3 e C4. Após serem introduzidas na análise multivariada, apenas HGI na semana anterior, albumina sérica e C4 do LA foram independentemente correlacionadas ao episódio de PBE (p=0.05). A mortalidade hospitalar e durante o acompanhento foi de 33,3% e 53,8% para o grupo com PBE; 8,5% e 31,9% para o grupo sem PBE; respectivamente (p=0.01 e p=0.04). A probabilidade cumulativa de sobrevida foi significativamente menor no grupo com PBE. CONCLUSÕES: A PBE é uma complicação freqüente, depende, principalmente, da gravidade da doença hepática e é um marcador de prognóstico desfavorável nos pacientes com cirrose hepática.<br>BACKGROUND: Spontaneous Bacterial Peritonitis (SBP) is a common and potentially fatal complication of cirrhosis. Multiple variants of this infection have been described during the past decade. Few studies have investigated SBP in Brazil. MATERIAL AND METHOD: In order to investigate prospectively prevalence, predictive factors and prognosis of the episode of SBP, we studied 143 in and outpatients with cirrhosis admitted to HUCFF and HUPE between January, 1995 and January, 1996. All patients were submitted to a questionaire, physical examination, blood analysis and abdominal paracentesis with ascitic fluid analysis. They were followed for a mean follow-up period of 4 months and survival was determined. RESULTS: The prevalence of SBP was 20%. Culture-positive SBP, Culture-negative Neutrocytic Ascites and Bacterascites were identified in 24%, 66% and 10%, respectively. After uni - and multivariate analysis, only anterior gastrointestinal hemorrhage, serum albumin and ascitic fluid C4 reached statistical significance (p=0.05) as predictive factors for the development of the SBP. The in-hospital and follow-up mortality rates were 33.3% and 53.8% for the SBP patients and 8.5% and 31.9% for the non-SBP patients, respectively (p=0.01 and p=0.04). The cumulative probability of survival in the SBP group was significantly lower than the probability of the non-SBP group (p=0.05). CONCLUSIONS: We conclude that SBP is a frequent complication, depends of the severity of liver failure and is a marker for poor prognosis in patients with liver cirrhosis

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. © 2013 .1814852Afdhal, N.H., The natural history of hepatitis C (2004) Semin Liver Dis, 24 (SUPPL. 2), pp. 3-8Fattovich, G., Giustina, G., Degos, F., (1997) Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients (1997) Gastroenterology, 112, pp. 463-472Veldt, B.J., Heathcote, E.J., Wedemeyer, H., Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis (2007) Ann Intern Med, 147, pp. 677-684Alves de Mattos, A., Zambam de Mattos, A., Treatment of HCV infection in patients with cirrhosis (2010) Ann Hepatol, 9 (SUPPL.), pp. 80-83Shiratori, Y., Ito, Y., Yokosuka, O., Antiviral therapy for cirrhotic hepatitis C: association with reduced hepatocellular carcinoma development and improved survival (2005) Ann Intern Med, 142, pp. 105-114Bruno, S., Stroffolini, T., Colombo, M., Sustained virological response to interferon-alpha is associated with improved outcome in HCV-related cirrhosis: a retrospective study (2007) Hepatology, 45, pp. 579-587Miyake, Y., Iwasaki, Y., Yamamoto, K., Meta-analysis: reduced incidence of hepatocellular carcinoma in patients not responding to interferon therapy of chronic hepatitis C (2010) Int J Cancer, 127, pp. 989-996Manns, M.P., McHutchison, J.G., Gordon, S.C., Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial (2001) Lancet, 358, pp. 958-965Bruno, S., Shiffman, M.L., Roberts, S.K., Efficacy and safety of peginterferon alfa-2a (40kD) plus ribavirin in hepatitis C patients with advanced fibrosis and cirrhosis (2010) Hepatology, 51, pp. 388-397Schalm, S.W., Weiland, O., Hansen, B.E., Interferon-ribavirin for chronic hepatitis C with and without cirrhosis: analysis of individual patient data of six controlled trials. Eurohep Study Group for Viral Hepatitis (1999) Gastroenterology, 117, pp. 408-413Heathcote, E.J., Shiffman, M.L., Cooksley, W.G., Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis (2000) N Engl J Med, 343, pp. 1673-1680Camma, C., Giunta, M., Andreone, P., Craxi, A., Interferon and prevention of hepatocellular carcinoma in viral cirrhosis: an evidence-based approach (2001) J Hepatol, 34, pp. 593-602Zhang, C.H., Xu, G.L., Jia, W.D., Li, J.S., Ma, J.L., Ge, Y.S., Effects of interferon treatment on development and progression of hepatocellular carcinoma in patients with chronic virus infection: a meta-analysis of randomized controlled trials (2011) Int J Cancer, 129, pp. 1254-1264Ghany, M.G., Nelson, D.R., Strader, D.B., Thomas, D.L., Seeff, L.B., American Association for Study of Liver Diseases. An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases (2011) Hepatology, 54, pp. 1433-1444Craxì, A., Pawlotsky, J.M., Wedemeyer, H., EASL Clinical Practice Guidelines: management of hepatitis C virus infection (2011) J Hepatol, 55, pp. 245-264D'Amico, G., Garcia-Tsao, G., Pagliaro, L., Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies (2006) J Hepatol, 44, pp. 217-231Poordad, F., McCone, J., Bacon, B.R., Boceprevir for untreated chronic HCV genotype 1 infection (2011) N Engl J Med, 364, pp. 1195-1206Bacon, B.R., Gordon, S.C., Lawitz, E., Boceprevir for previously treated chronic HCV genotype 1 infection (2011) N Engl J Med, 364, pp. 1207-1217Zeuzem, S., Andreone, P., Pol, S., Telaprevir for retreatment of HCV infection (2011) N Engl J Med, 364, pp. 2417-2428Jacobson, I.M., McHutchison, J.G., Dusheiko, G., Telaprevir for previously untreated chronic hepatitis C virus infection (2011) N Engl J Med, 364, pp. 2405-2416Ferenci, P., Fried, M.W., Shiffman, M.L., Predicting sustained virological responses in chronic hepatitis C patients treated with peginterferon alfa-2a (40 kD)/ribavirin (2005) J Hepatol, 43, pp. 425-433de Segadas-Soares, J.A., Villela-Nogueira, C.A., Perez, R.M., Nabuco, L.C., Brandão-Mello, C.E., Coelho, H.S., Is the rapid virologic response a positive predictive factor of sustained virologic response in all pretreatment status genotype 1 hepatitis c patients treated with peginterferon-alpha2b and ribavirin (2009) J Clin Gastroenterol, 43, pp. 362-366Giannini, E.G., Basso, M., Savarino, V., Picciotto, A., Predictive value of on-treatment response during full-dose antiviral therapy of patients with hepatitis C virus cirrhosis and portal hypertension (2009) J Intern Med, 266, pp. 537-546Hezode, C., Dorival, C., Zoulim, F., Safety of Telaprevir or Boceprevir in combination with Peginterferon alfa/ribavirin, in cirrhotic non responders. 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Detection of hepatitis C virus RNA by in situ hybridization in paraformaldehyde fixed biopsies

Fourteen hepatitis C virus (HCV) chronically infected patients were submitted to routine liver biopsy for histological evaluation. Liver samples were assayed to HCV-RNA by in situ hybridization, using digoxigenin labeled probe. HCV genotypes were found to be predominantly type 1 (71.4%), followed by genotype 3 (21.4%), and genotype 2 (7.2%). Alanine-aminotransferase levels were raised in 10 patients. The histopathological scores were minimal (21.4%), mild (57.2%), and moderate (21.4%). Viral RNA was detected in liver cells from nine patients (64.3%). ISH method provides localization and poor confirmation of HCV RNA in the liver tissue of HCV chronic patients

Geographic distribution of hepatitis C virus genotypes in Brazil

Brazil is a country of continental dimension with a population of different ethnic backgrounds. Thus, a wide variation in the frequencies of hepatitis C virus (HCV) genotypes is expected to occur. To address this point, 1,688 sequential samples from chronic HCV patients were analyzed. HCV-RNA was amplified by the RT-PCR from blood samples collected from 1995 to 2000 at different laboratories located in different cities from all Brazilian States. Samples were collected in tubes containing a gel separator, centrifuged in the site of collection and sent by express mail in a refrigerated container to Laboratório Bioquímico Jardim Paulista, São Paulo, SP, Brazil. HCV- RNA was extracted from serum and submitted to RT and nested PCR using standard procedures. Nested PCR products were submitted to cycle sequencing reactions without prior purification. Sequences were analyzed for genotype determination and the following frequencies were found: 64.9% (1,095) for genotype 1, 4.6% (78) for genotype 2, 30.2% (510) for genotype 3, 0.2% (3) for genotype 4, and 0.1% (2) for genotype 5. The frequencies of HCV genotypes were statistically different among Brazilian regions (P = 0.00017). In all regions, genotype 1 was the most frequent (51.7 to 74.1%), reaching the highest value in the North; genotype 2 was more prevalent in the Center-West region (11.4%), especially in Mato Grosso State (25.8%), while genotype 3 was more common in the South (43.2%). Genotypes 4 and 5 were rarely found and only in the Southeast, in São Paulo State. The present data indicate the need for careful epidemiological surveys throughout Brazil since knowing the frequency and distribution of the genotypes would provide key information for understanding the spread of HCV

Demographic and anthropometrical analysis and genotype distribution of chronic hepatitis C patients treated in public and private reference centers in Brazil

Hepatitis C virus (HCV) infection is a serious public health problem, since 80% to 85% of HCV carriers develop a persistent infection that can progress into liver cirrhosis and hepatocarcinoma. Considering that the response of hepatitis C patients to combination therapy with interferon and ribavirin depends on HCV characteristics as well as on host features, we made a retrospective analysis of demographic and anthropometrical data and HCV genotype distribution of chronic hepatitis C patients treated in public and private reference centers in Brazil. The medical records of 4,996 patients were reviewed, 81% from public and 19% from private institutions. Patients' median age was 46 years, and there was a higher prevalence of male (62%) and white patients (80%). The analysis of HCV-infecting strains showed a predominance of genotype 1 (64%) over genotypes 2 and 3. The patients' mean weight was 70.6 kg, and 65% of the patients weighed less than 77kg. Overweight and obesity were observed in 37.8% and 13.6% of the patients, respectively. Since a body weight of 75 kg or less has been considered an independent factor that significantly increases the odds of achieving a sustained virological response, the Brazilian population seems to have a more favorable body weight profile to achieve a sustained response than the American and European populations. The finding that 65% of chronic hepatitis C patients have a body weight of 77 kg or less may have a positive pharmacoeconomic impact on the treatment of genotype 1 HCV patients with weight-based doses of peginterferon