Hepatitis B virus genotype E detected in Brazil in an African patient who is a frequent traveler.

Genotype E of hepatitis B virus (HBV) has not been described in Brazil and is found mainly in Africa. Genotype A is the most prevalent in Brazil, and genotypes B, C, D, and F have already been reported. We report here an HBV genotype E-infected patient and some characterization of surface (S) protein, DNA polymerase (P) and precore/core (preC/C) coding regions based on the viral genome. The patient is a 31-year-old black man with chronic hepatitis B who was born and raised in Angola. He has been followed by a hepatologist in São Paulo, Brazil, since November 2003, and he is a frequent traveler to Latin America, Africa, and Europe. In 2003, he was diagnosed with HBV infection and started treatment with lamivudine with the later addition of adefovir dipivoxil. No known risk factor was identified. Serologically, he is HBsAg and anti-HBe positive, but HBeAg and anti-HBs negative. DNA sequence analysis of the S/P region confirmed that this patient is infected with genotype E, subtype ayw4. The preC/C region showed G1896A and G1899A mutations but no mutations in the basal core promoter. Nucleotide substitutions common in genotype E were also observed (C1772, T1858 and A1757). Although this is not an autochthonous case and there is no evidence of further spread, the description of this case in Brazil highlights the current risk of viral genotypes spreading with unprecedented speed due to constant travel around the world.

Re-treatment of chronic hepatitis C patients after relapse: efficacy of peginterferon-alpha-2a (40 kDa) and ribavirin.

We conducted a randomized multinational study to determine whether 48 weeks of re-treatment with peginterferon-alpha-2a (40 kDa) plus ribavirin would induce a sustained virological response (SVR) in relapsed chronic hepatitis C patients. Patients who had previously relapsed during 24 weeks of untreated follow-up, after having achieved an end-of-treatment virological response with 24 weeks of peginterferon-alpha-2a (40 kDa)/ribavirin combination therapy, within a phase III trial, were studied. Although the recommended dosage was the same as that used at the end of the initial trial, adjustments were permitted. Data on serious adverse events, or adverse events that resulted in dose reductions or discontinuations, were collected. Following re-treatment, the overall SVR rate in the 64 patients was 55%. The SVR rates in patients infected with hepatitis C virus (HCV) genotype 1 and non-1 genotypes were 51% and 63%, respectively. Early (week 12) virological responses were seen in 39 patients (61%) and were predictive of an SVR. Re-treatment was well tolerated. The most frequent adverse events recorded were fatigue (5%) and abdominal pain (3%). Dosages of peginterferon-alpha-2a (40 kDa) and/or ribavirin were modified because of adverse events in 3% and 13% of patients, and because of laboratory abnormalities in 23% and 5% of patients, respectively. Thus, a 48-week course of peginterferon-alpha-2a (40 kDa) plus ribavirin induces an SVR in 55% of patients who relapsed during follow-up after 24 weeks of combination therapy. Physicians should not hesitate to offer re-treatment to patients who relapse after an initial, 24-week course of combination therapy, or who have prematurely stopped treatment because, for example, of laboratory abnormalities.

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.

Early mortality in liver transplantation: bilirubin as predictor of outcome.

The shortage of donor organs and the long waiting lists have increased the need to better select liver transplant candidates using predictors of success. We reviewed the results of 29 liver transplantations performed from January 2002 to February 2003 analyzing the correlations with early mortality (30 days) of patient data, pretransplant laboratory data, warm ischemia time, intraoperations blood unit transfusions, and postoperative complications of prolonged mechanical ventilation, dialysis, and infection. Overall early mortality was 27.6% and 44% in fulminant hepatic failure (n = 9), there were four retransplants with one death, and two intraoperative deaths. Only pretransplant bilirubin (P =.045) and postoperative lactate levels (P =.002) were significantly different between alive versus dead patients. In this small population bilirubin was more related to death than the MELD score. Lactate levels, nonspecific predictor of death in shock syndromes were probably related to septic complications.

Thoracoscopy and talc poudrage in the management of hepatic hydrothorax.

STUDY OBJECTIVE: To determine indications, limitations, morbidity and mortality of surgical thoracoscopy for management of hepatic hydrothorax, a rare, but often recurrent, complication in cirrhotic patients. PATIENTS AND METHODS: From May 1985 through May 1999, 10 men and 8 women, with a mean age of 57.6 years (range, 26 to 76 years), underwent 21 therapeutic thoracoscopies to achieve pleurodesis by application of talc. RESULTS: The procedure was effective in 10 of 21 procedures. There were four recurrences (19. 1%) that were retreated, with only one being successful. In this specific group, we detected high morbidity (57.1%) and mortality (38.9%) during the follow-up period of 3 months. Diaphragmatic defects were localized and closed five times (23.8%). Hospital stay was approximately 15 days (range, 5 to 41 days). CONCLUSION: The procedure appears to be indicated for these fragile patients, especially when medical therapy fails. Immediate efficacy was 47.6%, increasing to 60% with videothoracoscopy and suture of the diaphragmatic defect. However, morbidity and mortality were high.

Estimated Prevalence of Viral Hepatitis in the General Population of the Municipality of São Paulo, Measured by a Serologic Survey of a Stratified, Randomized and Residence-Based Population.

The present study was done to estimate the prevalence of Hepatitis A (HAV), B (HBV), C (HCV), and E (HEV) infection in the general population residing in the municipality of São Paulo, and to evaluate the level of knowledge related to the various modes of infection transmission by and protection against the different viruses. Blood samples and health questionnaires were collected from 1,059 individuals. The study design used an inductive method of predictive statistical inferences through randomized sampling stratified by Sex, age and residence region. The estimated prevalence rated found were: Hepatitis A = 66.59% (63.75%-69.44% CI); Hepatitis B = 5.94% (4.50%-7.35%); Hepatitis C = 1.42% (0,70%-2.12%); Hepatitis E = 1.68% (0.91%-2.46%). The frequency of hepatitis was similar in males and females. HAV showed an estimated prevalence of 56.16% in the population up to 17 years old, increasing to 65.30% in individuals between 18 and 29 years. The infection reached its peak of 90% in individuals 40 years of age or older. The study showed a greater tendency of dissemination of HBV among the population between 15 and 17 years. This specific age group showed an estimated prevalence of active infection of 1.04% (0.43%-1.65% CI), and also demonstrated an ascending level of acquired immunity with an estimated prevalence of 4.90% (3.60%-6.20% CI). HCV demonstrated an estimated prevalence of 1.42% (0.70%-2.12% CI). This specific infection occurred more frequently among adults 30 years of age or older, with the prevalence reaching a peak of 3.80% among the group aged 50 to 59 years. HEV showed zero prevalence among the age group between 2 and 9 years. This was followed by a slightly ascending rate starting from age 10, with an estimated prevalence of 1.05% (0.94%-3.04% CI) among those 10 to 14 years of age. This infection reached its peak of 3.00% (0.55%-6.74% CI) at the age of 60 years or older. Individuals with lower educational levels had a higher tendency of acquiring HAV and HCV, while there was no statistically significant difference for this parameter related to HBV and HEV. HBV occurred more frequently among inhabitants of the northern region of the city. All other hepatitis forms occurred at similar frequencies among the five regions of the city. Among the population, 1.90% (1.08%-2.72% CI) demonstrated an elevated hepatic enzyme with no serologic evidence indicating the cause was the viruses studied. This observation suggests the presence of other hepatic diseases, possibly including other viral diseases. It was also estimated that 75.12% of the city's population did not know the modes of transmission of hepatitis viruses and 76.70% did not know how to prevent them. This clearly suggests the need for a full-scale education program combined with public health measures regarding prevention of all forms of vial hepatitis.

Sclerotherapy of bleeding esophageal varices in schistosomiasis. Comparative study in patients with and without previous surgery for portal hypertension.

Ninety-seven patients with bleeding esophageal varices due to mansonic schistosomiasis were treated with endoscopic sclerotherapy. Seventy-five patients (Group I) had previously undergone surgery for portal hypertension and presented with bleeding recurrence. Twenty-two patients (Group II) had not undergone surgical treatment. The sclerotherapy technique employed was intravascular (IV) injections of ethanolamine in 40 patients and paravascular (PV) in 57 patients. Of a total of 38 (39%) patients who had bleeding recurrence, 27 (36%) were from Group I and 11 (50%) from Group II (p less than 0.005). Over a follow-up period of 48 to 132 months, 367 sessions of sclerotherapy were carried out in the 72 remaining patients from Group I (4.93 +/- 2.05). The remaining 16 patients from Group II needed 121 (7.56 +/- 2.70) sessions of sclerotherapy (p less than 0.001). Thus, sclerotherapy was effective in the control of rebleeding in 73 (97.3%) patients from Group I and 16 (72.7%) from Group II (p less than 0.05). We conclude that previous surgical treatment for portal hypertension in patients with mansonic schistosomiasis, greatly benefits treatment of rebleeding esophageal varices by endoscopic sclerotherapy. This is probably due to the lower portal pressure after splenectomy.

Heparin response and clearance in acute and chronic liver disease.

Patients with liver disease are at risk of bleeding due to abnormalities of the clotting system although they must be anticoagulated if they require haemodialysis or haemoperfusion. The anticoagulant of choice is heparin. In this study we have investigated heparin kinetics in patients with fulminant hepatic failure (FHF) after a single intravenous dose of heparin (2,500 units) and found there was an increased clearance of heparin whether measured by its anti-Xa effect (t 1/2 = 27.8 +/- 2.9 min compared to t 1/2 = 50.2 +/- 2.7 min in normal controls p less than 0.001) or by the whole blood activated clotting time (t 1/2 = 23.7 +/- 2.2 min compared to t 1/2 = 37.0 +/- 2.0 min p less than 0.001). There was a decreased peak level of heparin measured by anti-Xa effect (peak level in FHF = 0.48 +/- 0.05 u/ml and in controls = 0.69 +/- 0.04 u/ml, p less than 0.02), but an increased sensitivity to heparin (sensitivity in FHF = 0.072 +/- 0.011 sec/unit, in controls 0.033 +/- 0.003 sec/unit, p less than 0.001). Patients with FHF had very low levels of antithrombin III (AT III), but there was no correlation between this and any parameters of heparin effect or clearance. In a group of patients with chronic liver disease heparin kinetics did not differ from controls despite low levels of AT III. The changes in heparin kinetics in FHF are likely to be complex with the balance between the proteins that act as cofactors, (e.g. AT III) and the proteins that have heparin neutralising activity, controlling the response of added heparin.

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.

A study of chromosomes of schistosomiasis patients under oxaminiquine (UK 4271) treatment.

Blood samples from 24 patients infested with Schistosoma mansoni were drawn immediately before and 2 days after the administration of a single therapeutic dose of 12-15 mg/kg oral oxaminiquine. Two-day lymphocyte cultures were obtained and about 100 mitoses from each blood sample were analyzed for chromosome aberrations. No significant differences were observed between the "before" and "after" cultures in the frequencies of aberrations resulting from spindle, chromatidic, or chromosome events. It is concluded that there is no reason to fear harmful effects on the chromosomes of patients from treatment with oxaminiquine.