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Biomedical subjects

R Paraná

Publications and source records attributed to R Paraná.

At least 19 recordsLinked to original sources
PubMed2006

Peginterferon alfa-2a (40KD) (PEGASYS) plus ribavirin (COPEGUS) in retreatment of chronic hepatitis C patients, nonresponders and relapsers to previous conventional interferon plus ribavirin therapy.

Peginterferon alfa plus ribavirin is currently the treatment of choice for chronic hepatitis C. Peginterferon alfa-2a (40KD) plus ribavirin has given an overall sustained virological response of 18% in F3/F4 previous nonresponder US patients. We evaluated the effectiveness of peginterferon alfa-2a (40KD) plus ribavirin in Brazilian patients who were relapsers or nonresponders to previous interferon-based therapy. One-hundred-thirty-four patients with biopsy-proven chronic hepatitis C, HCV RNA positive, elevated ALT and who were either relapsers (n=37) or nonresponders (n=97) to at least 24 weeks of conventional interferon/ribavirin therapy were retreated with peginterferon alfa-2a (40KD) 180mg/qw and ribavirin 800 mg bid for 48 weeks. Efficacy was assessed as virological response (defined as undetectable HCV RNA) at the end of treatment (EoT) and at the end of follow-up (SVR - Sustained Virological Response). Safety assessments consisted of clinical and laboratory evaluations. In the patient sample, 72% were genotype 1 and 34% were cirrhotic. In an intention-to-treat analysis, relapser patients showed 78% EoT response and 51% SVR. Nonresponders showed 57% EoT response and 26% SVR. Positive predictive factors of SVR were non-1 genotype and relapser state. Six percent of the patients interrupted treatment because of adverse events and 45% had dose reduction (mainly associated with leucopenia and anemia). Brazilian patient relapsers and nonresponders to conventional interferon and ribavirin treatment can achieve a sustained virological response when retreated with peginterferon alfa-2a (40KD) and ribavirin. The safety profile is similar to that of naive patients.

Adult↗
PubMed2004

Seroprevalence of hepatitis B and C in the Western Brazilian Amazon region (Rio Branco, Acre): a pilot study carried out during a hepatitis B vaccination program.

In 1999, on the occasion of the application of the first vaccine dose during the state vaccination campaign against hepatitis B virus (HBV), 390 individuals from the town of Rio Branco, Acre, aged two or more years were selected for the determination of the seroprevalence of HBV and HCV. HBV markers (HBsAg, anti-HBs, and anti-HBc IgG) were determined on this occasion and anti-HBs antibodies were also assessed 30 days after the third vaccine dose. At the time of vaccination, 39% of the individuals were still susceptible to HBV, while 61% presented serologic evidence of previous HBV contact or previous vaccination. The individuals with previous HBV contact were significantly older (p<0.001) than those without HBV markers. Of the 192 individuals who returned for reexamination, 30 days after the third dose, 158 (82.3%) had received three vaccine doses, and only 60 (31.2%) belonged to the group without HBV markers. In these individuals, the seroconversion rate after the third dose was 92% (55/60). In conclusion, we found considerable HBV in this population, indicating the need for pursuing the immunization programs. We also found high rates of vaccination coverage in the Western Brazilian Amazon region.

Adolescent↗
PubMed2003

Comparative study of hepatitis C virus genotypes 1 and 3 in Salvador, Bahia Brazil.

UNLABELLED: Hepatitis C virus displays a high degree of genetic mutation, with considerable heterogeneity, motivating clinical and biomolecular investigations. It is necessary to understand the effects of genotypes on the course of the disease, as well as their peculiarities at the regional level. OBJECTIVE: The study objective was to compare epidemiological, biochemical and histological aspects of hepatitis C virus genotypes 1 and 3 in Salvador, Bahia. STUDY DESIGN: Data were collected retrospectively from outpatient medical records. MATERIALS AND METHODS: 127 patients with positive anti-HCV results were selected, based on detectable RNA-HCV (RT-PCR) of genotypes 1a, 1b and 3a. RESULTS: Thirty-nine (30.7%) individuals were infected by subtype 1a, 45 (35.4%) by subtype 1b and 43 (33.9%) by subtype 3a. Most (73.2%) patients were male, with an average age of 47.8 years. The subtype 1b-infected patients had the highest average age (512 +/-11.17; P=0.09). The use of illicit injected drugs was more frequent among subtype 3a infected individuals when compared with genotype 1 (6/43; 14% and 3/84; 3.6%, respectively; P=0,06). No significant differences were found for other epidemiological characteristics. Average values for GT, AST, ALT and ferritin did not differ between the groups (64, 78, 109, 276, respectively). Thyroid dysfunction occurred in 7/30 (23.3%) of those infected by genotype 3 (P=0.05). Cryoglobulinemia was also more frequent in this group (5/13, 38%, P=0.02). Most patients presented limited necro-inflammatory activity, stages 2 and 3 by the METAVIR Classification. In some cases, dissociation was noticed between inflammatory activity and fibrosis. No significant differences were found in the histopathological findings of the various genotypes. Younger patients had a significantly smaller degree of necrosis in stomatocytosis (P=0.032) and fibrosis (P=0.012). Intense parenchymatous activity and lymphoid follicles were more frequent among alcohol consumers (P=0.06 and P=0.04, respectively). CONCLUSIONS: In Bahia, genotype 3 dissemination seems to be associated with illicit drug use. The disease evolution depends on a function of complex interactions between virus and host. Age and alcohol consumption stand out as important variables in the development of cirrhosis.

Adolescent↗
PubMed2001

HCV infection in northeastern Brazil: unexpected high prevalence of genotype 3a and absence of African genotypes.

The genomic diversity of HCV embraces 6 genotypes and at least 52 subtypes with clinical and epidemiological correlations. There is a paucity of studies assessing HCV genotypes and biomolecular epidemiology in Brazil. We studied genotype distribution and epidemiological aspects in 232 HCV carriers, 133 (57.9%) males and 99 (42.1%) females, followed in the liver disease referral unit in Salvador, BA, northeastern Brazil. All of them were anti-HCV positive by 3rd generation ELISA assay, and HCV-RNA positive by RT-PCR. Genotyping was performed by INNOLIPA. Assessment of risk factors for HCV infection showed that 93 (40%) had past blood transfusion, 14 (6%) intravenous drug use, 19 (8%) inhalation of cocaine, 28 (12%) tattooing, 15 (7%) were health care workers, 5 (2%) had reused disposable syringes, 5 (2%) had multiple risk factors and in 53 (23%) no risk factor was determined. Genotype 1a was observed in 75 (32%), 1b in 72 (31%), 3a in 61 (26%), 2ab in 14 (6%); 5 (2.5%) had mixed genotypes and 5 (2.5%) were undetermined. Patients with genotype 1 had a higher mean age (P < 0.05) and no particular risk factors were associated with a specific genotype. Genotype 1 largely predominates in northeast Brazil followed by genotype 3 which, in this population, does not seem to be related to intravenous drug abuse, in contrast to some European studies. Although 80% of the Salvador population comprises African-Brazilians, no African genotype was identified, which may mean that HCV was introduced into this region via European immigration. This study demonstrated some peculiarities of HCV epidemiology in Brazil and strongly suggests that HCV introduction to this region was probably related to European immigration.

Adult↗
PubMed2001

Schistosomiasis mansoni and viral B hepatitis in woodchucks.

BACKGROUND/AIMS: An interaction between human schistosomiasis and viral hepatitis B has often been suggested, but never established. The experimental investigation has been hampered by the lack of a suitable model. Only woodchucks are susceptible to both Schistosoma mansoni and a B-like hepatitis virus (WHV) infections. This study explores the relevance of this unique model regarding hepatitis/schistosomiasis interactions. METHODS: Woodchucks (Marmota monax and Marmota marmota) were infected with: (a), S. mansoni; (b), WHV; or (c), both S. mansoni and WHV. RESULTS: Following the experimental parasitic infection of woodchucks, with or without WHV, schistosomiasis presented a peculiar and severe course in early infection, involving mostly the intestines. Subsequently, the intestinal and hepatic lesions underwent considerable modulation and the periovular granulomas decreased in size and number, while the parasitic infection tended to self-cure within the 9 months following infection. Nine woodchucks inoculated with the hepatitis virus alone presented with several degrees of acute and chronic hepatitis, with one of them dying of hepatocarcinoma 1 year after inoculation. Four woodchucks with concomitant viral and schistosome infections presented with a simple additive pattern of lesions, without any evidence of modification or aggravation of either one of the two infections. Similarly, no significant impact of schistosomiasis on WHV serum markers could be seen. CONCLUSIONS: Schistosomiasis and viral hepatitis in woodchucks run parallel courses, with neither apparent special histological features derived from the association of the two conditions, nor modulation of WHV replication. Schistosomiasis itself, however, was observed to run a peculiar course in the woodchuck. The present data are important for consideration in further experiments exploring the interplay between schistosomiasis and viral hepatitis induced liver damage in this unique experimental host.

Animals↗
PubMed2001

Effect of interferon-alpha on experimental septal fibrosis of the liver - study with a new model.

Interferon-alpha is used in antiviral therapy in humans, mainly for viral hepatitis B and C. An anti-fibrotic effect of interferon has been postulated even in the absence of anti-viral response, which suggests that interferon directly inhibits fibrogenesis. Rats infected with the helminth Capillaria hepatica regularly develop diffuse septal fibrosis of the liver, which terminates in cirrhosis 40 days after inoculation. The aim of this study was to test the anti-fibrotic effect of interferon in this experimental model. Evaluation of fibrosis was made by three separate methods: semi-quantitative histology, computerized morphometry and hydroxyproline measurements. Treatment with interferon-alpha proved to inhibit the development of fibrosis in this model, especially when doses of 500,000 and 800,000 IU were used for 60 days. Besides confirming the anti-fibrotic potential of interferon-alpha on a non-viral new experimental model of hepatic fibrosis, a clear-cut dose-dependent effect was observed.

Animals↗
PubMed2001

Comparative study of bacterial infection prevalence between cirrhotic patients with and without upper gastrointestinal bleeding.

Bacterial infection is a frequent complication in patients with chronic liver disease, mainly during the advanced stages. There is evidence that the main factors that contribute to a predisposition to infection in cirrhotic patients are related to hepatic failure with consequent immunodeficiency. Invasive procedures (diagnostic or therapeutic) can predispose to bacterial infections, and upper gastrointestinal bleeding (UGB) is considered a potentially important risk factor. A group of cirrhotic patients (child B and C Pugh groups) were evaluated retrospectively by chart reviews regarding the prevalence of bacterial infection during hospitalization to determine whether UGB was a risk factor. An infection was considered present if a specific organ system was identified or if fever (> 38(o)C) persisted for more than 24 hours with associated leukocytosis. Spontaneous bacterial peritonitis was based on classical criteria. Eighty-nine patients were evaluated. Fourty-six patients presented with UGB, and 43 patients had no UGB (control). There were infections recorded in 25/46 (54%) patients with UGB, and 15/43 (35%) in those without UGB (p=0.065). The ratio of the number of infections/admitted patients, was significantly larger in the group with UGB (0.78 +/- 0.89 vs. 0.39 +/- 0.62; p=0.028) since patients had more than one infection. In the UGB group compared to non UGB group, ascites was more frequent (67% vs. 42%; p=0.027); they were more likely to have undergone endoscopic procedures (p<0.001) and the mean +/- SD for platelets count was smaller (96,114 +/- 57,563 vs 145,674 +/- 104,083; p=0.007). The results show that UGB is an important contribution to bacterial infection among Child B and C cirrhotic patients.

Bacterial Infections↗
PubMed2000

Subacute thyroiditis during treatment with combination therapy (interferon plus ribavirin) for hepatitis C virus.

Autoimmune thyroiditis has been frequently reported during interferon monotherapy for hepatitis C, but there are few reports concerning subacute thyroiditis. Recently, combination therapy of IFN plus ribavirin has become the preferred therapeutic schedule for chronic hepatitis C. Similarly to interferon monotherapy, there are no reports concerning subacute thyroiditis during combination therapy. We described four episodes of subacute thyroiditis occurring in three patients during antiviral combination therapy. All patients had symptoms compatible with hyperthyroidism, which could be misdiagnosed as IFN side-effects. The antiviral treatment was continued in all three patients and thyroid function increased progressively with pharmacological treatment for hyperthyroidism. We concluded that subacute thyroiditis may be a complication of combination antiviral therapy and should be investigated in patients presenting with compatible symptoms, in order to differentiate from IFN side-effects.

Adult↗
PubMed2000

Severe strongyloidiasis during interferon plus ribavirin therapy for chronic HCV infection.

Ribavirin is a nucleoside analogue, recently introduced in hepatitis C virus (HCV) therapy, that has postulated immunomodulatory and immunosuppressive action. Strongyloidiasis is an helmintic infection caused by Strongyloides stercoralis, endemic in tropical countries. Severe strongyloidiasis has been demonstrated after immunosuppression by corticosteroids evolving some fatal cases. Here, we describe two cases of severe strongyloidiasis coincident with ribavirin plus interferon therapy for treating HCV infection. The review of our monotherapy protocol with interferon did not disclose any case of symptomatic strongyloidiasis pointing to a possible role of ribavirin in modifying immune response to S. stercoralis. We propose a careful screening for S. stercoralis before initiating ribavirin therapy or even empiric antihelmintic treatment.

Adult↗
PubMed2000

Hepatic capillariasis in rats: a new model for testing antifibrotic drugs.

Rats infected with the helminth Capillaria hepatica regularly develop septal hepatic fibrosis that may progress to cirrhosis in a relatively short time. Because of such characteristics, this experimental model was selected for testing drugs exhibiting antifibrosis potential, such as pentoxifylline, gadolinium chloride and vitamin A. Hepatic fibrosis was qualitatively and quantitatively evaluated in liver samples obtained by partial hepatectomy and at autopsy. The material was submitted to histological, biochemical and morphometric methods. A statistically significant reduction of fibrosis was obtained with pentoxifylline when administered intraperitoneally rather than intravenously. Gadolinium chloride showed moderate activity when administered prophylactically (before fibrosis had started), but showed a poor effect when fibrosis was well advanced. No modification of fibrosis was seen after vitamin A administration. Hydroxyproline content was correlated with morphometric measurements. The model appears to be adequate, since few animals die of the infection, fibrosis develops regularly in all animals, and the effects of different antifibrotic drugs and administration protocols can be easily detected.

Animals↗
PubMed2000

Hepatitis C virus genotypes in a northeastern area of Brazil.

We used a reverse transcription-polymerase chain reaction (RT-PCR) to obtain the genotypes of circulating hepatitis C virus (HCV) in patients from a Gastro-Hepatology Unit in the city of Salvador (Bahia State) in northeastern Brazil. Viral RNA was detected in 83 (65.4%) of 127 anti-HCV seropositive serum samples. Positivity was significantly associated with alterations in levels of aspartate aminotransferase and alanine aminotransferase (P < 0.05). Genotyping of HCV was performed by RT-PCR using genotype-specific primers from the core region: 24.1% were infected with subtype 1a, 38.6% with 1b, 3.6% with 2, 21.7% with 3a, and 12.0% with a mixed genotype. There was no difference in genotype distribution when compared with results from other Brazilian locations. Surprisingly, the high frequency of genotype 3 in Brazilian samples continues to be different from that reported around the world and warrants further investigation.

Adolescent↗
PubMed2000

New hepatitis viruses.

Three new hepatitis viruses are reviewed; Hepatitis E Virus (HEV), Hepatitis G Virus (HGV), and Transfusion Transmitted Virus (TTV). Only HEV has been clearly associated with liver damage. It is transmitted by the fecal-oral route and tends to occur in poor socio-economic conditions. Acute disease is diagnosed by the presence of anti-HEV IgM antibodies in the serum. Hepatitis G virus and TTV are transmitted parenterally. HGV is the same agent as GBV-C. Although it is hepatotropic, and high levels of viremia may occur, pathogenicity to the liver has not been proven. TTV may also be transmitted by the fecal-oral route. It is abundant in liver tissue but, like HGV, pathogenicity has not been proven.

DNA Virus Infections↗
PubMed2000

Thyroid disease in HCV carriers undergoing antiviral therapy with interferon plus ribavirin.

High prevalence of thyroid autoantibodies, with or without overt thyroiditis, has been described in hepatitis C patients, particularly in those undergoing alpha-interferon treatment. The aim of this study was to describe the frequency and clinical outcome of thyroid disease in a cohort of HCV carriers before and during combination therapy with interferon plus ribavirin. Between May, 1997, and May, 1999, 111 previously untreated (naive) patients were treated with a-interferon plus ribavirin for 6 or 12 months. Of those, 67 (60%) patients were male and 44 (40%) female. Thyroid function was evaluated in all patients by testing free T4, TSH and antiTPO within 30 days prior to treatment, 90 days after treatment was initiated, and 6 months after treatment was concluded. Abnormal thyroid tests were observed in 4 (3.6%) patients--1 male and 3 female--before the onset of antiviral treatment. Three patients were already undergoing T4 replacement due to Hashimoto thyroiditis and 1 patient had positive antiTPO with normal free T4 and TSH. All 4 patients completed the treatment regime for HCV, but required hormone replacement. Among the patients with a normal thyroid function test prior to treatment (107 cases), 5 (4.6%) developed thyroid test abnormalities; 2 patients had hypothyroidism due to autoimmune thyroiditis; 1 patient became positive for antiTPO antibodies but thyroid function remained normal, and 2 patients had subacute thyroiditis. Four of these patients (80%) were female and 1 was male (20%). A family history of thyroid disease was strongly predictive of thyroid abnormalities during antiviral treatment. In conclusion, there is a low prevalence of thyroid function abnormalities in HCV carriers with no prior antiviral treatment. Family history of thyroid disease reinforces the special attention to thyroid abnormality development before considering antiviral therapy. Subacute thyroiditis during combination therapy was observed, but its pathogenesis is still unknown. Evaluation of thyroid function during and after antiviral treatment is strongly recommended because thyroid related symptoms can be easily misinterpreted as medication side effects.

Adult↗
PubMed1999

Acute sporadic non-A, non-B hepatitis in Northeastern Brazil: etiology and natural history.

In a 4-year follow-up study, patients with acute sporadic non-A, non-B (NANB) hepatitis were evaluated to determine the etiology and natural history of the disease. Acute hepatitis C virus (HCV) was detected in 13 of 43 (30%) of patients, anti-hepatitis E virus (HEV) IgG in 5 (12%), and 25 (58%) were considered non-A-E. The HCV RNA was detected in all HCV patients but none of the non-A-E cases. The initial clinical and biochemical presentation of the HCV and non-A-E cases was quite similar, although 2 of the non-A-E patients had severe disease. The 5 patients who were found to be anti-HEV IgG-reactive recovered within 6 months of follow-up. Of the 13 HCV cases, alanine transaminase (ALT) levels returned to normal in 7 (53. 8%), while 6 (46.2%) continued to show abnormal ALT after 6 months of follow-up. However, 9 (69.2%) of them remained HCV-RNA-positive, denoting virological/biochemical dissociation. Long-term follow-up showed a reappearance of HCV RNA in 2 of the 4 patients who were in virological remission performing 84% of chronicity rate. Acute non-A-E hepatitis patients were less likely to evolve toward chronicity, as compared with acute HCV cases (16% vs. 84%; P =.0001). Only 4 (16%) of the non-A-E patients were hepatitis G virus (HGV)-RNA-positive. Concerning risk factors for acquiring parenterally transmitted viruses, tattooing was the only one that could be associated with HCV transmission (P =.002). No risk factors could be identified for putative non-A-E virus transmission. Liver biopsies performed for chronic HCV patients showed a variable degree of inflammation, while the non-A-E patients presented less severe histological disease.

Acute Disease↗