Hepatitis: Cavalheiro Nde P

Cavalheiro Nde P. · Hepatitis Laboratory, Infectious Diseases Department, School of Medicine, University of São Paulo, São Paulo, SP, Brazil. · Rev Inst Med Trop Sao Paulo. · Pubmed #18026632 links to  free full text

Abstract: It is generally agreed that the hepatitis C virus (HCV) can be efficiently transmitted parenterally, although data on viral transmission by sexual or non-sexual intrafamilial contact are conflicting. Since data collection began in 1989, the first study dealt with the risk of sexual transmission among multiple sex partners. Other investigations followed, emphasizing that risk increases in specific groups such as patients co-infected with HIV and HBV, sex workers, homosexuals, illicit drug users and patients attended at sexually transmittable disease clinics. The question arises as to what might be the risk for monogamous heterosexuals in the general population, in which one of the partners has HCV? The literature provides overall rates that vary from zero to 27%; however, most studies affirm that the chances of sexual transmission are low or almost null, with rates for this mode fluctuating from zero to 3%. Intrafamilial transmission is strongly considered but inconclusive, since when mentioning transmission between sex partners within the same household, specific situations also should be considered, such as the sharing of personal hygiene items, like razorblades, toothbrushes, nail clippers and manicure pliers, which are important risk factors in HCV transmission. In this review, we discuss the hypotheses of sexual and/or intrafamilial transmission.

de Araujo ES, Cavalheiro Nde P, Cubero Leitao RM, Borges Tosta RA, Barone AA. · Departamento de Moléstias Infecciosas e Parasitárias, FMUSP, São Paulo, SP, Brasil. · Rev Inst Med Trop Sao Paulo. · Pubmed #12048543 links to  free full text

Abstract: The analysis of 58 patients with chronic hepatitis C without cirrhosis and treated with interferon-alpha demonstrated that hepatitis C viral (HCV) load does not correlate with the histological evolution of the disease (p = 0.6559 for architectural alterations and p = 0.6271 for the histological activity index). Therefore, the use of viral RNA quantification as an evolutive predictor or determinant of the severity of hepatitis C is incorrect and of relative value. A review of the literature provided fundamental and interdependent HCV (genotype, heterogeneity and mutants, specific proteins), host (sex, age, weight, etc) and treatment variables (dosage, time of treatment, type of interferon) within the broader context of viral kinetics, interferon-mediated immunological response (in addition to natural immunity against HCV) and the role of interferon as a modulator of fibrogenesis. Therefore, viral load implies much more than numbers and the correct interpretation of these data should consider a broader context depending on multiple factors that are more complex than the simple value obtained upon quantification.

Cavalheiro Nde P, Santos AC, Melo CE, Morimitsu SR, Barone AA. · Department of Infectious Diseases, Clinical Hospital, University of São Paulo, SP, Brazil. · Braz J Infect Dis. · Pubmed #19219272 links to  free full text

Abstract: Though HCV infection is a serious public health problem, some aspects of its biology are still not well understood, such as its transmission through seminal fluid and sexual transmission. We looked for HCV in the semen of infected patients. Thirteen patients were included. Semen fractions (seminal plasma, leukocytes and spermatozoa) were separated with 45% and 90% Percoll gradients. The HCV-RNA in blood and semen fractions was extracted using the same protocol (AMPLICOR Roche) and was detected using the qualitative Roche Amplicor test and by agarose gel electrophoresis, with ethidium bromide staining. The mean age of the patients was 40.7 years. Risk factors for the acquisition of HCV included injectable and inhaled drug use in six (42.8%), blood transfusion in four (28.6%), and no risk factors in four (28.6%) patients. Genotype 1 was detected in 62% of the patients, followed by genotype 3 in 23% and genotype 2 in 15%. All blood samples were positive, regardless of the technique used for detection. All semen samples identified by Roche Amplicor and analyzed by agarose gel electrophoresis were negative. Among the 52 semen samples (total and fractions) identified by the Roche Amplicor method, 45 (87%) were inhibited. A negative result was recorded for one (1.9%) total semen sample, one (1.9%) leukocyte and four (7.7%) seminal plasma fractions. Only one (1.9%) sample of the spermatozoon fraction was positive. The results obtained suggested false-negative reactions for the semen samples.

Mendes-Correa MC, Widman A, Brussi ML, Guastini CF, Cavalheiro Nde P, Melo CE, Barone AA, Gianini RJ. · Casa da AIDS, Division of Infectious Diseases, Hospital das Clinicas, São Paulo University, São Paulo, SP, Brazil. · Rev Inst Med Trop Sao Paulo. · Pubmed #18813760 links to  free full text

Abstract: Hepatitis C virus (HCV) is an important factor contributing to morbidity and mortality in patients co-infected with HIV and HCV. In addition, liver biopsy is an important tool in the clinical management of these patients. Although liver biopsy is controversial, it is recommended for all patients. Data regarding the clinical and histological characteristics of these patients are scarce not only in Brazil but in Latin America as a whole. With the goal of better understanding these characteristics and the benefit of liver biopsy indications in this disease setting, data collected from 234 patients followed from 1996 to 2004 at Casa da AIDS, São Paulo, were analyzed. The following variables were extracted from the patients' medical files at the time of liver biopsy: sex, age, hepatitis C infection risk factors, hepatitis C infection duration, ALT levels, CD4+ T cell counts, history of alcohol abuse, history of antiretroviral therapy, HCV genotype, and liver histological alterations. CONCLUSIONS: 1 - Hepatitis C virus 1 and 3 were the most frequently identified genotypes and were diagnosed in 72% and 25.5% of cases respectively; 2 - Structural liver alterations were found to be mild or absent in 48.2% (113/234) of the analyzed patients; 3 - Fifty-three patients (23%) had normal ALT levels and 4 - Significant liver architectural changes (F2-F3) were evident in 22.5% of the patients with normal ALT levels.

Cavalheiro Nde P, Filgueiras TC, Melo CE, Morimitsu SR, de Araújo ES, Tengan FM, Barone AA. · Hepatitis Laboratory, Department of Infectious Diseases, Clinical Hospital, University of São Paulo, Av. Dr. Eneas de Carvalho Aguiar 500, São Paulo, SP, Brazil. · Braz J Infect Dis. · Pubmed #17962872 links to  free full text

Abstract: Although hepatitis C is mainly hepatotropic, some studies suggest that hepatitis C virus (HCV) infects peripheral blood mononuclear cells (PBMC), using them as a reservoir, which might contribute to the development of resistance to treatment. Fifty-four hepatitis-C patients, who had been submitted to treatment, were selected. Blood samples were collected on the same day for the detection of HCV RNA in serum and PBMC by PCR, using the Amplicor HCV 2.0 assay (Roche Diagnostics). HCV genotyping was performed using the INNO-LiPA HCV kit (Versant, Bayer Diagnostics). HCV RNA was detected in both serum and PBMC in 35 (64%) patients and no RNA in 16 (29.6%). Disagreement between the serum and PBMC results was observed for three patients (5.6%), with HCV RNA being detected in PBMC but not in serum. Four months later, new serum and PBMC samples were collected from one of these patients and HCV RNA was detected in both samples, showing that PBMC can reveal signs of a lack of response to treatment. We conclude that the absence of HCV in the serum of patients with chronic hepatitis C by the end of treatment does not mean that there is no circulating virus. HCV in mononuclear cells may be an indicator of the persisting infection.

de Vasconcelos RR, Tengan FM, Cavalheiro Nde P, Ibrahim K, Pereira H, Barone AA. · Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Uberlândia, Uberlândia, MG. · Rev Soc Bras Med Trop. · Pubmed #17160319 links to  free full text

Abstract: To assess the factors associated with the development of moderate and severe fibrosis, the medical records of 426 patients with chronic hepatitis C virus infection attended at the Infectious and Parasitic Diseases Clinic of the University of São Paulo Faculty of Medicine from January 1 to December 31, 2000 were reviewed. Of the patients included in the study, 56.3% were male and 43.7%, female. Patient age ranged from 18 to 69 years. Blood transfusion was the most frequent form of hepatitis C virus transmission, detected in 128 (30%) cases, and no risk factor was detected in 187 (43.9%) patients. Patient distribution regarding architectural changes observed in a liver biopsy was: grade 0 (14.1%); grade 1 (51.2%); grade 2 (20.6%); grade 3 (8%); grade 4 (6.1%). Multivariate analysis revealed a positive correlation between fibrosis severity and age greater than 40 years at the time of the liver biopsy, serum albumin levels below normal lower limits, gamma-glutamyltransferase levels equal to or higher than twice upper normal limits, platelet numbers less than 150,000/mm(3) and high necroinflammatory activity. The data obtained were inconclusive regarding a possible correlation between severity of fibrosis and alcoholism.

Pereira HM, Cavalheiro Nde P, Tengan FM, Melo CE, Mello ES, Barone AA. · Department of Infectious and Parasitary Diseases, University of São Paulo, São Paulo, SP, Brazil. · Rev Inst Med Trop Sao Paulo. · Pubmed #16302106 links to  free full text

Abstract: Hepatitis C virus infection evolves progressively persisting in the majority of patients (85%). Most patients have high ALT (alanine aminotransferase) levels and approximately 25% normal ALT. The latter are usually female and there is no association between genotype and severity of hepatic lesion. Histologic analysis usually shows small lesion and absence or low amount of fibrosis, despite cirrhosis having been reported. Aiming at assessing prevalence, demographic, genotypical and anatomopathological characteristics in patients with normal ALT levels, we have carried out a study of 68 chronic hepatitis C patients between January 1997 and April 2000. There was a prevalence of 13.8% chronic hepatitis C patients with normal ALT levels, 45.6% of which were male and 54.4% female, the mean age being 38 +/- 13 years. We found a predominance of genotype 1 in 84.7% of the patients, genotype 2 in 6.8% and genotype 3 in 10.7%. In 52.9% of the cases liver biopsies revealed liver reaction, periportal activity score 0-1 was observed in 85.3% of the patients and score 2-4 was seen in 14.7%. Structural activity score 0-1 was seen in 73.5% of the patients and score 2-4 in 26.5% of them. Periportal activity > or = 2 and structural activity > 1 was seen in 29%, but steatosis was not seen in 73.5%. Our results suggest the need to revisit for liver biopsy practice in patients with chronic hepatitis C and normal transaminases.

Navarro RM, Mendes-Correa MC, Cavalheiro Nde P, Barone AA. · Laboratório de Hepatites (LIM-47), Instituto de Medicina Tropical de São Paulo, Av. Dr. Enéas de Carvalho Aguiar 470, 05403-000 São Paulo, SP, Brazil. · Rev Inst Med Trop Sao Paulo. · Pubmed #15729469 links to  free full text

Abstract: During the year of 2001, a retrospective, descriptive study in order to determine the influence of the antiretroviral therapy received by 111 HIV-HCV coinfected patients who had undergone at least one liver biopsy was conducted, 74 of them were treated with a protease inhibitor regimen (WPI), and 37 with a non-protease inhibitor regimen (NPI). The main characteristics found were: a young patient population (mean age 41 years old in both groups), composed in most part of male individuals (74.3% WPI and 51.4% NPI) with previous risk factors for both infections (WPI 93.2% and NPI 89.2%). The most significant findings included AIDS-defining disease (WPI 18.9% and NPI 13.5% of the cases), elevated hepatic enzyme levels (WPI: SGOT 52.1 and NPI 53.2), absence of liver disease-related symptoms (16.2% for both groups), average CD4 count > 350 for both groups (WPI 362.2 and NPI 378.1), predominantly low-grade fibrosis in both populations (0-2 in 63.6% of WPI patients and in 80% of NPI patients), with necro-inflammatory activity ranging from 5-7 in 51.3% and 42.9% of WPI patients and NPI patients, respectively. It is suggested a sequential biopsy to better evaluate the evolution of the hepatic disease, according to the HAART regimen received.

Barone AA, Tosta RA, Tengan FM, Marins JH, Cavalheiro Nde P, Cardi BA. · Department of Infectious and Parasitic Diseases, Medical School, University of São Paulo, São Paulo, SP, Brazil. · Braz J Infect Dis. · Pubmed #15286876 links to  free full text

Abstract: A follow-up study was made of 94 chronic hepatitis C patients at a hepatitis clinic in Brazil, after interferon alpha (IFN-alpha) therapy, to determine the influence of anti-interferon antibodies on treatment outcome. Patients diagnosed as having chronic hepatitis C, confirmed by PCR (HCV RNA) and liver biopsy, were treated with interferon alpha 2a or 2b for at least six months, and were followed up for 24 weeks after termination of treatment in order to assess biochemical, virological and clinical pathology responses. Only 6% of the 94 patients developed anti-IFN antibodies, 70% presented a biochemical response and 23% maintained a sustained virological response. Clinical evaluation revealed that in only 2 patients was there progression of fibrosis; the necro-inflammatory score indicated that 72% maintained the same activity, 12% had worsening necro-inflammatory activity, and the remaining 16% had decreased activity. There was no significant correlation of demographic and laboratory variables with levels of anti-interferon antibodies. Similarly, biochemical and virological responses were not influenced by anti-interferon antibodies. Multivariate analysis by logistic regression revealed that clinical pathological parameters, staging and necro-inflammatory activity did not influence the response to the virus.

Cavalheiro Nde P, Barone AA, Tengan FM. · Hepatitis Laboratory, University Hospital, Faculty of Medicine, University of São Paulo, Brazil. · Int J Infect Dis. · Pubmed #12718840 No free full text.

Abstract: OBJECTIVE: To investigate the prevalence of the different types of hepatitis C virus (HCV) in a population of chronic HCV carriers using the Murex HCV serotyping 1-6 assay. METHODS: All serum samples from these patients had a positive nested PCR HCV reaction. The sera were submitted to ELISA, modified, for the identification of antibodies against HCV serotypes 1, 2, 3, 4, 5 and 6 (Murex HCV serotyping 1-6 assay). RESULTS: The viral serotype was identified in 166 (75.8%) of the 219 patients, 108 (65.11%) males and 58 (34.9%) females. Patient age ranged from 12 to 73 years, with a mean of 41.1 years. The form of acquisition of the disease most frequently reported was blood transfusion. The results showed a predominance of type 1 (70.0%), followed by type 3 (22.3%) and type 2 (4.2%). CONCLUSION: Samples presenting low and very close optical density readings may lead to discrepant diagnoses concerning HCV serotypes and should be confirmed by genotyping. The serotyping can be useful in clinical practice and can be of help in establishing the prognosis of the disease, also favoring epidemiologic studies independently of the technology required for genotyping tests.