Response to treatment with interferon-alpha and ribavirin in patients with chronic Hepatitis C virus genotypes 2 and 3 depends on the degree of hepatic fibrosis

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

High incidence of tuberculosis in patients treated for hepatitis C chronic infection

AbstractBrazil is one of the 22 countries that concentrates 80% of global tuberculosis cases concomitantly to a large number of hepatitis C carriers and some epidemiological risk scenarios are coincident for both diseases. We analyzed tuberculosis cases that occurred during α-interferon-based therapy for hepatitis C in reference centers in Brazil between 2001 and 2012 and reviewed their medical records. Eighteen tuberculosis cases were observed in patients submitted to hepatitis C α-interferon-based therapy. All patients were human immunodeficiency virus-negative. Nine patients (50%) had extra-pulmonary tuberculosis; 15 (83%) showed significant liver fibrosis. Hepatitis C treatment was discontinued in 12 patients (67%) due to tuberculosis reactivation and six (33%) had sustained virological response. The majority of patients had a favorable outcome but one died. Considering the evidences of α-IFN interference over the containment of Mycobacterium tuberculosis, the immune impairment of cirrhotic patients, the increase of tuberculosis case reports during hepatitis C treatment with atypical and severe presentations and the negative impact on sustained virological response, we think these are strong arguments for latent tuberculosis infection screening before starting α-interferon-based therapy for any indication and even to consider IFN-free regimens against hepatitis C when a patient tests positive for latent tuberculosis infection

Hepatitis C virus treatment in advanced cirrhosis: impact in natural history, safety and efficacy

Introdução: A cirrose hepatica pela hepatite C (HCV) e a maior indicacao de transplante hepatico (TxH) na maioria dos centros do ocidente. A recorrencia virologica da infeccao e praticamente universal e a velocidade de progressao da fibrose apos o transplante e maior que no imunocompetente. Embora estudos previos tenham relatado pequenas taxas de resposta e aumento da incidencia de infeccoes bacterianas, o tratamento antiviral pode ser alternativa viavel para individuos com cirrose avancada, mas ainda sem possibilidade de TxH. Objetivos: Determinar a eligibilidade dos pacientes com cirrose pelo HCV referidos para transplante hepatico. Avaliar a seguranca do tratamento e o impacto na historia natural da doenca. Avaliar a eficacia do tratamento e os fatores associados a resposta. Material e Metodos: Estudo prospectivo, que avaliou pacientes com cirrose por HCV referidos para centro de transplante por descompensacao previa e/ou comprometimento da funcao hepatica. Criterios de inclusao para tratamento: idade entre 18 e 70 anos; Child-Pugh <11; MELD &#8804;18; plaquetas &#8805;30.000/mm3; neutrofilos &#8805;750/mm3; hemoglobina &#8805;8 g/dL; creatinina&#8804;1,5 mg/dL; ausencia de descompensacao vigente. O tratamento foi proposto com interferon peguilado &#61537;-2b (0,75-1,5 &#61549;g/Kg) e ribavirina (500-1250 mg/d) de acordo com parametros clinicos e laboratoriais estabelecidos para este estudo. Os individuos tratados e os nao tratados foram acompanhados em dois periodos, P1 e P2, sendo que P1 se estendia da inclusao ate tres meses apos o tratamento e P2 do final de P1 ate o final do seguimento. Os desfechos clinicos em cada periodo foram comparados para avaliar o impacto do tratamento na historia natural. Resultados: Foram avaliados 123 pacientes. Noventa pacientes constituiram a casuistica, 39 incluidos para tratamento (56,4% do sexo masculino, 35,9% Child B/C, MELD 11,6 &#61617; 2,5) e 51 nao tratados (60,8% do sexo masculino, 78,4% Child B/C, MELD 13,9 &#61617; 4,1). Vinte e dois pacientes (56%) completaram o tratamento. Suspensao prematura foi necessaria em 14 (35,9%), principalmente por descompensacao apos quadro infeccioso (n=5). Doze (30,8%) apresentaram infeccao e 14 (35,9%) tiveram descompensacao no P1. A taxa de resposta virologica sustentada (RVS) foi de 20,5%. Resposta virologica rapida (RVR) se associou a obtencao de RVS por intencao de tratamento (100% vs. 21,7%; p<0,001) e per protocol, com valor preditivo positivo de 85,7% e valor preditivo negativo de 92,3%. Aumento da dose de interferon (55,5% vs. 100%; p<0,05) se associou a suspensao do tratamento. Ao se comparar os pacientes tratados com os nao tratados, observou-se que o grupo tratado apresentou incidencia (30,8% vs. 49%; p=0,07) e numero de infeccoes (0,5 &#61617; 0,9 vs. 0,7 &#61617; 1,1; p=0,27) no P1 semelhante a coorte nao tratada, mas a incidencia (35,9% vs. 64,6%; p<0,05) e o numero de descompensacoes (0,7 &#61617; 1,1 vs. 1,7 &#61617; 2,2; p<0,05) permaneceram menores. A mortalidade em todo o seguimento foi menor no grupo tratado (21% vs. 51,2%; p<0,05). Em analise de regressao logistica, somente menores valores de albumina (OR=0,24; p=0,007) foram preditores da ocorrencia de infeccoes e apenas a classe de Child (OR=3,75; p=0,004) se associou independentemente ao risco de descompensacao da cirrose no P1. O unico preditor independente de mortalidade foi a pontuacao de Child na ultima avaliacao disponivel (OR=1,91; p=0,034). Conclusoes: O tratamento foi possivel em parcela significativa de pacientes e, embora tenha apresentado tolerancia e resposta modestas, nao teve impacto independente na ocorrencia de infeccoes, descompensacoes ou na sobrevida. O bom desempenho da RVR visto nesta casuistica pode auxiliar a decisao de manutencao do tratamentoBV UNIFESP: Teses e dissertaçõe

Spontaneous bacterial peritonitis: How to deal with this life-threatening cirrhosis complication?

Tarsila CR Ribeiro1, Julio MF Chebli2, Mario Kondo1, Pedro Duarte Gaburri3, Liliana Andrade Chebli2, Ana Cristina Amaral Feldner11Division of Gastroenterology, Department of Medicine of University Federal de S&amp;atilde;o Paulo, UNIFESP, EPM, S&amp;atilde;o Paulo, S&amp;atilde;o Paulo, Brazil; 2Division of Gastroenterology, Department of Medicine of University Federal de Juiz de Fora, UFJF, Juiz de Fora, Minas Gerais, Brazil; 3Liver Unit Coordinator of Santa Casa de Miseric&amp;oacute;rdia de Juiz de Fora, Minas Gerais, BrazilAbstract: Spontaneous bacterial peritonitis (SBP) is one of the most common and life-threatening complications of cirrhosis. It occurs in 10% to 30% of patients admitted to hospital and recent studies tend to demonstrate that SBP incidence seems to be decreasing in its frequency. A bacterial overgrowth with translocation through the increased permeable small intestinal wall and impaired defense mechanisms is considered to be the main mechanism associated with its occurrence. The Gram-negative aerobic bacteria are the major responsible for SBP episodes and Gram-positive bacteria, mainly Staphylococcus aureus, are being considered an emergent agent causing SBP. The prompt diagnosis of SBP is the key factor for reduction observed in mortality rates in recent years. The clinical diagnosis of SBP is neither sensitive nor specific and the search for new practical and available tools for a rapid diagnosis of SBP is an important endpoint of current studies. Reagent strips were considered a promising and faster way of SBP diagnosis. The prompt use of empirical antibiotics, mostly cefotaxime, improves significantly the short-term prognosis of cirrhotic patients with SBP. The recurrence rate of SBP is high and antibiotic prophylaxis has been recommended in high-risk settings. Unfortunately, the long-term prognosis remains poor.Keywords: cirrhosis, ascites, diagnosis, peritonitis, treatmen

Plasma gamma-glutamyltransferase alteration in hepatic schistosomiasis bears no correlation with either the parasitic load or ultrasound alterations

Background - Liver disorders are the major manifestations of schistosomiasis mansoni. Factors that account for increased concentrations of cholestasis-indicating enzymes in the hepatosplenic form of the disease are unknown. Objective - To assess the correlation between increased gamma-glutamyltransferase serum levels and both the parasitic load and ultrasound alterations in patients with schistosomiasis. Patients and methods - Twenty-five patients with the chronic form of schistosomiasis were assessed for the presence or absence of increased enzymatic levels, for the parasitic load (low x medium/high) and for ultrasound parameters. Furthermore, analysis of prothrombin time and a platelet count were performed. Results - Of the 25 patients, 13 showed increased gamma-glutamyltransferase plasma levels. No significant correlation was found between increased gamma-glutamyltransferase levels and the parasitic load, or between increased enzyme levels and ultrasound alterations. Nor did the prothrombin index or the platelet count differ between the two groups (normal gamma-glutamyltransferase levels and increased gamma-glutamyltransferase levels). Conclusion - The parasitic load explains no rise in gamma-glutamyltransferase plasma levels in patients with the chronic form of schistosomiasis, and conventional ultrasound is not a sensitive method to detect the alteration suggested by the increased enzyme level in those patients.Racional - As alterações hepáticas constituem as mais importantes manifestações da esquistossomose mansônica. Não são conhecidos fatores que expliquem elevação sérica de enzimas indicadoras de colestase na forma hepatoesplênica da doença. Objetivo - Avaliar a correlação entre elevação da gama-glutamiltransferase sérica e a carga parasitária e alterações ultra-sonográficas em pacientes esquistossomóticos. Casuística e método - Foram avaliados 25 pacientes portadores da forma crônica pura da esquistossomose, quanto a presença ou não de elevação enzimática, quanto a carga parasitária (baixa x média/alta) e quanto a parâmetros ultra-sonográficos. Foi realizada, ainda, análise do índice de protrombina e contagem de plaquetas. Resultados - Dos 25 pacientes, 13 apresentavam elevação da gama-glutamiltransferase sérica. Não houve correlação significativa entre elevação de gama-glutamiltransferase e carga parasitária, ou entre elevação da enzima e alterações ultra-sonográficas. O índice de protrombina e a contagem de plaquetas também não foram diferentes entre os dois grupos (gama-glutamiltransferase normal e gama-glutamiltransferase elevada). Conclusão - A carga parasitária não explica o aumento da gama-glutamiltransferase sérica em pacientes portadores de esquistossomose e a ultra-sonografia convencional não é método sensível para detectar alteração sugerida pela elevação da enzima nestes pacientes.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de MedicinaUNIFESP, EPM, Depto. de MedicinaSciEL

Does hepatitis B virus coinfection have any impact on treatment outcome in hepatitis C patients on hemodialysis?

Background. HBV/HCV coinfection is a common finding among hemodialysis patients. However, there is scarce information concerning the impact of HBV coinfection on the response to treatment of HCV-infected patients on hemodialysis.Aim. We aimed to compare the rate of sustained virologic response (SVR) to treatment with interferon-alfa (IFN) between hemodialysis patients with HBV/HCV coinfection and those with HCV-monoinfection.Material and methods. HCV-infected patients on hemodialysis treated with IFN were included. Patients coinfected by HBV/HCV were compared to HCV-monoinfected patients, regarding clinical and biochemical features and rates of SVR.Results. One hundred and eleven patients were treated. HBV/HCV coinfection was observed in 18/111 patients (16%). Coinfected patients were younger (p = 002), had more time on dialysis (p = 0.05) and showed a tendency to present a higher prevalence of septal fibrosis (p = 0.06). The analysis by intention to treat showed SVR of 56% among coinfected patients and 18% in HCV-monoinfected patients (p = 0.004).Conclusion. In conclusion, end-stage renal disease patients with HBV/HCV coinfection exhibit higher rate of SVR to HCV treatment than HCV-monoinfected patients. It is possible that factors related to the host immune response and viral interaction could explain the better response observed among coinfected patients

Is early virological response as predictive of the hepatitis C treatment response in dialysis patients as in non-uremic patients?

Objective: the aim of the present study was to determine whether hepatitis C virus (HCV) RNA present at week 12 is a good predictor of the response to interferon (IFN) monotherapy in hemodialysis patients with hepatitis C.Methods: Hemodialysis patients with hepatitis C who were treated between 1997 and 2008 with IFN monotherapy for 48 weeks without dose reduction were included. the predictive value of HCV RNA at week 12 for achieving a sustained virological response (SVR) was determined.Results: Forty patients (mean age 47 +/- 9 years; 75% males and 80% with genotype 1) were included. Septal fibrosis or cirrhosis was observed in 38% of these patients. Twelve (30%) of the 40 patients achieved SVR. HCV RNA was undetectable at week 12 in 68%. the positive predictive value of HCV RNA at week 12 was 45% and the negative predictive value was 100%.Conclusions: the presence of HCV RNA at week 12 had a high negative predictive value for SVR in hemodialysis patients with chronic hepatitis C treated with IFN for 48 weeks. Therefore, if HCV RNA is detected at week 12, treatment should be discontinued due to the low probability of a sustained response. (0 2012 International Society for Infectious Diseases. Published by Elsevier B.V. All rights reserved

Acute exacerbation of chronic hepatitis B virus infection in renal transplant patients

Introduction: There is scarce information regarding clinical evolution of HBV infection in renal transplant patients. Aims: To evaluate the prevalence of acute exacerbation in HBV-infected renal transplant patients and its association with the time after transplantation, presence of viral replication, clinical evolution, and use of antiviral prophylaxis. Materials and methods: HBV infected renal transplant patients who underwent regular follow-up visits at 6-month intervals were included in the study. The criteria adopted to characterize exacerbation were: ALT >5 × ULN and/or >3 × baseline level. Predictive factors of exacerbation evaluated were age, gender, time on dialysis, type of donor, post-transplant time, ALT, HBeAg, HBV-DNA, HCV-RNA, immunosuppressive therapy, and use of antiviral prophylaxis. Results: 140 HBV-infected renal transplant patients were included (71% males; age 46 ±10 years; post-renal transplant time 8 ±5 years). During follow-up, 25% (35/140) of the patients presented exacerbation within 3.4 ±3 years after renal transplant. Viral replication was observed in all patients with exacerbation. Clinical and/or laboratory signs of hepatic insufficiency were present in 17% (6/35) of the patients. Three patients died as a consequence of liver failure. In univariate analysis variables associated with exacerbation were less frequent use of prophylactic/preemptive lamivudine and of mycophenolate mofetil. Lamivudine use was the only variable independently associated with exacerbation, with a protective effect. Conclusions: Acute exacerbation was a frequent and severe event in HBV-infected renal transplant patients. Prophylactic/preemptive therapy with antiviral drugs should be indicated for all HBsAg-positive renal transplant patients.Universidade Federal de São Paulo (UNIFESP) Division of GastroenterologyUniversidade Federal do Rio de Janeiro (UFRJ) Internal Medicine DepartmentUNIFESP, Division of GastroenterologySciEL