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.

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 percent 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 800mg 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 percent were genotype 1 and 34 percent were cirrhotic. In an intention-to-treat analysis, relapser patients showed 78 percent EoT response and 51 percent SVR. Nonresponders showed 57 percent EoT response and 26 percent 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 percent 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.

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.

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 percent (1,095) for genotype 1, 4.6 percent (78) for genotype 2, 30.2 percent (510) for genotype 3, 0.2 percent (3) for genotype 4, and 0.1 percent (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 percent), reaching the highest value in the North; genotype 2 was more prevalent in the Center-West region (11.4 percent), especially in Mato Grosso State (25.8 percent), while genotype 3 was more common in the South (43.2 percent). 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.

[The hepatitis B virus in alcoholic liver disease: its clinical and biochemical assessment]. / O vírus da hepatite B na doença hepática alcoólica: avaliação clínica e bioquímica.

The aim of our work was to study the prevalence of HBV markers in Alcoholic Liver Disease (ALD) by evaluating clinical and biochemical parameters that could further characterize the association. A prospective and sequential study of 107 patients with ALD was performed, including 83 cases of cirrhosis and 24 cases of alcoholic hepatitis. Daily ingestion of pure ethanol was of at least 70 gm for seven years or more and always associated with hepatocellular disfunction. According to the serological profile for HBV markers the patients were allocated to one of four groups: group I infected (positivity of HBsAg and anti-HBc); group II immunized (positivity of anti-HBs and anti-HBc); group III without HBV markers (negativity of HBsAg, anti-HBc and anti-HBs); group IV isolated anti-HBc. The prevalence of HBsAg positivity in ALD was high: 15.89% whereas immunity was low: 26.17% suggesting a great exposure to the virus and a deficient immunological response. No significant statistical differences were found among the three groups when clinical and biochemical parameters were individually considered. Nevertheless, when a Child/Campbell classification was applied, patients with ALD associated with HBV (group I) showed a significant difference, presenting a predominance of child C, with a bad prognosis.

[Long-term results of implantable automatic defibrillator in 43 patients. Analysis of predictive factors of the first electric shock]. / Résultats à long terme du défibrillateur automatique implantable chez 43 patients. Analyse des facteurs de prévision du premier choc électrique.

In order to identify patients who will receive an electric shock after implantation of an automatic fibrillator, the relationship between the time to the first shock and clinical and paraclinical characteristics were studied in 43 patients treated at the Lyon Cardiological Hospital between July 1987 and September 1991. The age of the patients was 49.5 +/- 16 years (mean + SD). Eighty two percent of patients were men and the average left ventricular ejection fraction was 38.5 +/- 16.8%. Four patients died in the peri-operative period. The average follow-up of the survivors was 22 months. During this period, 21 patients (53.8%) received an appropriate electric shock. Three patients died. The causal role of a malignant ventricular arrhythmia is discussed in one case. A second patient, who never had automatic fibrillation, died of cardiac failure. Finally, the third patient died of non-cardiac pathology. The 22 month actuarial survival rate was 86%. The probability of receiving an appropriate electric shock was 60%. Analysis of clinical and paraclinical features identified left ventricular dysfunction (ejection fraction less than 38%) and cardiac symptoms (Stage III dyspnoea of the NYHA classification) as being associated with earlier electric shocks. This association was even more clear cut in the group of patients with previous myocardial infarction. Therefore, patients with implantable automatic defibrillators for malignant ventricular arrhythmias receive appropriate electric shocks in over 50% of cases. Patients with symptoms of cardiac failure and low ejection fraction are particularly exposed especially when they have previous myocardial infarction.

Cryptogenic cirrhosis: clinico-biochemical comparison with alcoholic and viral etiologies.

Cryptogenic cirrhosis defines a group of undetermined etiology that would either be caused by factors as alcohol, virus and others or be due to still unknown etiological factors. To test these hypotheses we have looked for similarities or differences in clinico-biochemical presentation of 196 cases of alcoholic, viral and cryptogenic cirrhosis. Age, jaundice, spiders, palmar erythema and factor V showed a statistically significant difference of the cryptogenic cirrhosis when compared with both alcoholic and viral etiologies. On clinico-biochemical grounds it could be suggested that cryptogenic cirrhosis would constitute a discrete group, based on the following parameters: predominance of females, a more advanced age, less marked peripheral signs of chronic hepatic failure (jaundice, spiders and palmar erythema) besides milder alterations of laboratory liver function tests.

A randomized trial for the study of the elective surgical treatment of portal hypertension in mansonic schistosomiasis.

From 1977 to 1983, 94 patients with esophageal varices and gastrointestinal bleeding secondary to mansonic schistosomiasis were entered into a prospective randomized trial comparing the three operations mainly used in Brazil: esophagogastric devascularization associated with splenectomy (EGDS, 32 patients), classical splenorenal shunt (SRS, 32 patients), and distal splenorenal shunt (DSRS, 30 patients). The randomization was interrupted because of a significant incidence of portosystemic encephalopathy (PSE) in the SRS group (26%), as compared to the DSRS (7%) and EGDS (0%) groups. The rate of rebleeding was the same in the three groups, but the rate of failure, as defined by the presence of technical problems, postoperative complications, or death, was significantly higher in the SRS group. This 2-year follow-up shows that SRS should be abandoned in hepatosplenic schistosomiasis and that a comparison between DSRS and EGDS with a longer follow-up is urgently needed.

Praziquantel in the treatment of the hepatosplenic form of Schistosomiasis mansoni.

UNLABELLED: 40 patients with the hepatosplenic form of schistosomiasis mansoni were selected for this study. Among 29 patients submitted to oral endoscopy there were 28 in whom oesophageal varices were demonstrated and 20 out of 21 patients who presented gastrointestinal haemorrhage had been operated on. All patients received a single oral dose of 40 mg/kg b.w. of 2-cyclohexylcarbonyl-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-one (praziquantel, EMBAY 8440, Biltricide). Unwanted side effects were recorded when spontaneously reported. These were rather frequent but generally mild and disappeared within hours without additional medication. Comprehensive laboratory tests as well as ECG and EEG dit not show any significant changes. 27 patients were parasitologically followed up for 3-6 months; 26 of them were egg-negative. In the 18 patients who could be followed up for more than 6 months, the cure rate was 94.4%. CONCLUSION: praziquantel can be safely given also to patients with hepatosplenic complications.