Hoel Sette

Entecavir therapy for lamivudine‐refractory chronic hepatitis B: Improved virologic, biochemical, and serology outcomes through 96 weeks

In hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B patients who were refractory to current lamivudine therapy, switching to entecavir was superior to continued lamivudine at week 48 for histologic improvement, viral load reduction by polymerase chain reaction and alanine aminotransferase normalization. We assessed the efficacy, safety, and resistance profile of entecavir through 96 weeks of treatment. A total of 286 patients were randomized and treated with entecavir 1 mg (n = 141) or continued lamivudine 100 mg (n = 145). At week 52, 77 entecavir‐treated patients who had a protocol‐defined virologic response (HBV branched DNA [bDNA] < 0.7 MEq/mL but HBeAg‐positive) continued blinded therapy for up to 96 weeks. Patients were assessed for efficacy, safety, and emerging resistance. Cumulative proportions of all treated patients who achieved confirmed efficacy endpoints were also analyzed. Between week 48 and the end of dosing, the proportions of patients with HBV DNA <300 copies/mL by polymerase chain reaction increased from 21% to 40%, and alanine aminotransferase normalization (≤1× upper limit of normal) increased from 65% to 81%. In the second year, HBeAg seroconversion was achieved by 10% of patients. Of the 77 patients in the second year treatment cohort, entecavir resistance emerged in six patients, and seven experienced virologic breakthrough (five with genotypic resistance acquired before year 2). The safety profile of entecavir in the second year of therapy was consistent with that reported during year 1. Conclusion: Through 96 weeks of treatment, 1 mg entecavir resulted in continued clinical benefit in lamivudine‐refractory HBeAg‐positive chronic hepatitis B patients with a safety profile comparable to lamivudine. (HEPATOLOGY 2008.)

Efficacy and safety of entecavir in patients with chronic hepatitis B and advanced hepatic fibrosis or cirrhosis.

OBJECTIVE: The efficacy and safety of entecavir in patients with chronic hepatitis B and advanced liver fibrosis/cirrhosis was assessed from three large, randomized, multicenter, phase III studies.PATIENTS AND METHODS:These studies enrolled patients (≥16 yr) with chronic hepatitis B, elevated alanine aminotransferase (ALT) levels, and compensated liver disease. Two trials enrolled nucleos(t)ide-naive patients randomized to at least 48 wk of treatment with entecavir 0.5 mg/day or lamivudine 100 mg/day. The third trial randomized lamivudine-refractory patients to 48 wk of entecavir 1 mg/day or lamivudine 100 mg/day. In this post hoc descriptive analysis, the efficacy and safety in patients with advanced liver fibrosis/cirrhosis (Ishak fibrosis stages 4–6) were examined for consistency with those seen in the overall study populations.RESULTS: Of the 1,633 treated patients, 245 had advanced liver fibrosis/cirrhosis (120 entecavir and 125 lamivudine). Among entecavir-treated patients with advanced liver fibrosis, improvement in Ishak fibrosis was observed in 57% of nucleos(t)ide-naive hepatitis B e antigen (HBeAg)-positive patients, 59% of nucleos(t)ide-naive HBeAg-negative patients, and 43% of lamivudine-refractory HBeAg-positive patients versus 49%, 53%, and 33% of lamivudine-treated patients with advanced liver fibrosis. The overall trends in other histologic, virologic, biochemical, and serologic outcomes in entecavir- versus lamivudine-treated patients with advanced liver fibrosis/cirrhosis were consistent with those observed in the overall study populations in each trial. The treatment was well tolerated.CONCLUSION: These data confirm that the performance of entecavir relative to that of lamivudine in patients with advanced liver fibrosis/cirrhosis was consistent with the relationship observed in the overall treated population.

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.

Epidemiological aspects of acute viral hepatitis in São Paulo, Brazil

As few reports on the prevalence of each type of viral hepatitis have been published in our country, we studied 154 patients with acute viral hepatitis consecutively seen at the Liver Unit from November 1980 to November 1984. The frequency of hepatitis A, B and non-A, non-B was 52.6%, 27.3% and 20.1% respectively. Greater frequency in young people, previous contact with infected patients and ingestion of suspected foods were the predominant epidemiological features in the hepatitis A group. Hepatitis B was characterized by the parenteral, non-transfusional exposure, previous contact and a high occurence in health-care workers. A history of blood transfusion was a significant finding in the hepatitis non-A, non-B group. Finally, the routes of transmission were unknown in 30-40% of the three groups of patients.

Pharmacoeconomics applied to chronic hepatitis C

Life expectancy has increased over the last century as it had never been before. This is the result of a combination of many favorable variables such as level of education, improved socio-economic environment and development of medicine. However, new improvements demand heavy investment. Thus, the incorporation of medical technology became a health and economic issue. The pharmacoeconomic knowledge field is being developed to help in the analysis of medical costs and patient needs. The applies to hepatitic C, a common and chronic worldwide disease. In this article, the authors describe the rational behind this type of health economic analysis and review a hepatitis C model. Overall, in a non-Brazilian scenario, it was demonstrated that peginterferon alfa-2a (40KD) is cost effective in the treatment of HCV disease.