Severe thrombocytopenia in a patient with hepatitis C treated with eltrombopag from off-label drug use to on-label drug use: a case report.

INTRODUCTION: Off-label drug use refers to drug use beyond the specifications authorized for marketing. Eltrombopag is a new thrombopoietin receptor agonist which was used successfully in this critical case of thrombocytopenia associated with hepatitis C infection before it became an approved drug for such cases. CASE PRESENTATION: A 56-year-old Kuwaiti woman with hepatitis C virus infection was treated with pegylated interferon α-2a and ribavirin, laboratory test results prior to therapy were within normal values. After 4 weeks of that treatment, she developed neutropenia and severe thrombocytopenia. Her hepatitis C virus treatment was stopped for many years until eltrombopag was used as an off-label drug with an episode of severe thrombocytopenia. Her platelets count returned to normal level when triple therapy for hepatitis C virus was used successfully. CONCLUSIONS: An off-label drug should be used only when it is the best available drug, based on evidence from on-going multicenter trials. It could be life saving for some patients in critical situations. However, clinical use of eltrombopag later confirmed that it is a safe and effective drug for immune thrombocytopenic purpura or thrombocytopenia associated with hepatitis C virus infection.

Peginterferon alpha-2b plus ribavirin with or without amantadine [correction of amantidine] for the treatment of non-responders to standard interferon and ribavirin.

BACKGROUND: A significant proportion of hepatitis C patients treated with unmodified interferon plus ribavirin fail to respond. The optimal therapy for these patients has not been established yet. The objective of this study was to assess the efficacy and safety of peginterferon plus ribavirin with or without amantidine in such patients. METHODS: In this open-label, prospective controlled trial, a total of 63 patients were randomly divided into groups A and B with a ratio of 1:2. Group A (21 patients) received weekly peginterferon alpha-2b, 1.5 microg/kg concomitantly with ribavirin 1000-1200mg per day. Group B (42 patients) received peginterferon and ribavirin as in group A, plus amantadine [corrected] 200 mg per day. RESULTS: At the completion of treatment, serum levels of hepatitis C virus RNA were undetectable in 14% and 12% of patients in groups A and B, respectively (P=NS). Hepatitis C virus RNA remained undetectable 24 weeks after the end of treatment in one patient (5%) in group A and three patients (7%) in group B (P=NS). Sustained viral clearance was associated with sustained normalization of serum alanine aminotransferase level. Both drug regimens had similar side effect profiles. CONCLUSION: Peginterferon plus ribavirin therapy with or without amantadine [corrected] is associated with a low sustained virological response in patients who failed interferon and ribavirin combination therapy.

Peginterferon alfa-2b plus ribavirin for the treatment of chronic hepatitis C genotype 4.

BACKGROUND: The hepatitis C virus (HCV) genotype is an important predictive parameter for the success of pegylated interferon plus ribavirin therapy. To date, most published therapeutic trials have enrolled patients infected mainly with HCV genotypes 1, 2, and 3. Data regarding the responsiveness of genotype 4, the predominant type of HCV in the Middle East, are very limited. OBJECTIVE: To assess the efficacy of peginterferon alfa-2b in combination with ribavirin for the treatment of chronic hepatitis caused by HCV genotype 4. METHODS: Sixty-six treatment-naive patients infected with HCV genotype 4 were enrolled in this open label, prospective study. Cohort characteristics included the following: 48 M/18 F, mean age 45 +/- 9 years, and mean weight 74 +/- 8 kg. All patients had raised alanine aminotransferase (ALT) and were compensated. The mean pretreatment HCV-RNA level was 4.2 x 10(6) copies/ml (8.4 x 10(5) iu/ml) and median was 2.15 x 10(6) copies/ml. Twenty patients (29%) exhibited cirrhosis or severe fibrosis on pretreatment liver biopsy specimens. Participants were to receive peginterferon alfa-2b, 1.5 mcg/kg/wk plus ribavirin 1,000-1,200 mg/day for 48 wk. Patients were followed up for 24 wk after completing therapy. End of treatment viral response and sustained viral response (SVR) were defined as the absence of HCV-RNA from serum (<100 copies/ml) at 48 wk of treatment and at the end of follow-up, respectively. Data were analyzed on an intention-to-treat basis. RESULTS: End of treatment and sustained virologic response were 77% and 68%, respectively. Among patients with pretreatment HCV-RNA > or =2 x 10(6) SVR was 55% compared with SVR of 86% among patients with HCV-RNA < 2 x 10(6) (p= 0.05). Patients with cirrhosis or severe fibrosis had significantly lower SVR rate compared to those with mild or no fibrosis (29 vs 84%; p < 0.0002). Three patients (4%) discontinued therapy because of severe flu-like symptoms. Four patients developed hypothyroidism. Dose reduction of ribavirin and peginterferon alfa-2b was necessary in 15% and 6% of the patients, respectively. CONCLUSION: Peginterferon alfa-2b in combination with ribavirin is effective in the treatment of HCV genotype 4. The treatment was well tolerated by most of the patients.

Treatment of chronic hepatitis B with the sequential administration of interferon and lamivudine.

BACKGROUND/AIMS: Interferon monotherapy has been shown to induce a sustained viral response in 30-40% of patients with HbeAg-positive chronic hepatitis B infection. Similarly, lamivudine monotherapy causes HBeAg seroconversion in less than 20% of patients treated for one year. This study aims to assess the efficacy and safety of the sequential administration of interferon alfa-2a plus lamivudine to patients with chronic hepatitis B in comparison to lamivudine monotherapy. METHODOLOGY: Sixty-one patients with HbeAg-positive chronic hepatitis B infection and raised ALT were randomized to receive either interferon Alfa-2a, 4.5 million units daily for 16 weeks plus lamivudine 100 mg daily starting from week 5 and continuing for 48 weeks (Group A, n = 32) or lamivudine monotherapy for 48 weeks (Group B; n = 29). Patients were followed for 48 weeks after completion of therapy. RESULTS: HBeAg seroconversion to anti-HB +ve was observed in 2 (6.2%) patients in Group A. Both patients remained HBeAg negative and HBV-DNA negative throughout the follow-up phase. None of the group B patients seroconverted at the end of therapy or during follow-up (P = NS). All group A patients experienced at least one side effect and as a result, one dropped out. All group B patients completed the study without side effects. CONCLUSIONS: The sequential administration of interferon plus lamivudine was not superior to lamivudine monotherapy for the treatment of chronic hepatitis B and was associated with more side effects.