Hanneke van Soest

No beneficial effects of amantadine in treatment of chronic hepatitis C patients.

BACKGROUND Benefit of adding amantadine to antiviral therapy for hepatitis C is controversial. AIMS We aimed to examine whether such policy enhances sustained viral response in treatment-naïve patients. METHODS 297 naïve hepatitis C patients were randomized for treatment with amantadine 200mg or placebo, combined with weight-based ribavirin and 12-day high-dose interferon alpha-2b induction therapy, followed by PEG-interferon alpha-2b (1.5 microg/kg/week up to 26 weeks and thereafter, 1.0 microg/kg/week until week 52). Treatment was discontinued if hepatitis C virus (HCV) RNA was positive at week 24. RESULTS 49% of patients were (former) drug users. Genotype 1 occurred in 45%, high viral load in 70% and severe fibrosis/cirrhosis in 32%, without differences between amantadine or placebo groups. 90 patients prematurely discontinued treatment, mainly because of grade 3 or 4 toxicity. Intention-to-treat analysis revealed sustained viral response in 47% and 51% of amantadine and placebo groups (p=0.49). Amantadine did not enhance sustained viral response in patients with genotype 1 or high viral load nor did it improve primary non-response, breakthrough or relapse rates. Genotype non-1 and lower pre-treatment gamma GT levels were independent predictors for sustained viral response. CONCLUSION Adding amantadine to antiviral therapy of previously untreated chronic hepatitis C patients has no beneficial effects.

Suboptimal endogenous erythropoietin response in chronic hepatitis C patients during ribavirin and PEG interferon treatment.

Background During the treatment of hepatitis C, anaemia may necessitate pegylated-interferon and ribavirin dose reductions with reduced sustained viral response rates. Although erythropoietic growth factors are frequently used to improve anaemia, it is controversial whether endogenous erythropoietic response is insufficient under these circumstances. We aimed to identify risk factors for more pronounced anaemia and to evaluate endogenous erythropoietic response during antiviral therapy. Methods One hundred and forty-five naive chronic hepatitis C patients on pegylated-interferon–ribavirin treatment were evaluated for haemoglobin, haematocrit, serum ribavirin and erythropoietin levels. Results About 99% of patients developed anaemia, with maximal decrease in haemoglobin of 2.5±1.0 mmol/l (range 0.3–5.5 mmol/l). Older age, lower baseline creatinine clearance, higher baseline haemoglobin, more pronounced haemoglobin decrease after 2 weeks and higher week 24 serum ribavirin concentrations were independent risk factors for more pronounced anaemia. Serum erythropoietin levels increased from median 12 IU/l (range 4–63 IU/l) at baseline to 41 IU/l (range 12–683 IU/l) after 12 weeks of therapy and to 43 IU/l (range 7–3238 IU/l) at week 24 (P<0.001). Erythropoietin levels at baseline, week 12 and week 24 negatively correlated with haematocrit. The erythropoietic response to anaemia in our study population was significantly different from the normal human response to anaemia. Conclusion Older age, lower baseline creatinine clearance, higher baseline haemoglobin, more pronounced haemoglobin decrease after 2 weeks and higher week 24 serum ribavirin concentrations were independent risk factors for more pronounced anaemia during antiviral therapy. Endogenous erythropoietin production is suboptimal during antiviral therapy, supporting use of erythropoietic growth factors.

Influence of alpha-1 antitrypsin heterozygosity on treatment efficacy of HCV combination therapy

Background The role of heterozygosity for alpha-1 antitrypsin (A1AT) alleles in patients with chronic hepatitis C virus (HCV) is unclear. There is limited evidence to suggest that there is an increased prevalence of heterozygous A1AT carriers in HCV, but it is unclear how this affects treatment success. Aim To investigate the (i) prevalence of A1AT heterozygosity among two HCV cohorts and (ii) its effect on treatment outcome. Methods We performed a retrospective cohort study using two different cohorts. Cohort 1 consisted of 678 German HCV patients, 507 of them were treated for HCV with standard therapy. Cohort 2 consisted of 370 Dutch HCV patients of which 252 were part of a clinical trial (treatment with amantadine or placebo, in combination with pegylated interferon &agr;-2b and ribavirin) whereas 37 HCV patients received standard therapy. We analyzed A1AT status using direct sequencing of the A1AT gene (cohort 1) or isoelectric focusing of serum (cohort 2). In addition, we measured A1AT serum levels (cohort 2). Results In total, we included 1048 HCV patients; 986 (94%) were wildtype [protease inhibitor (Pi) MM], whereas 61 (6%) were heterozygous for a mutant A1AT allele (41 Pi MS, 20 Pi MZ). Mean A1AT serum levels (370 patients) were lower in A1AT heterozygous patients (1.68 vs. 1.36 g/l), (P<0.05) compared with wildtypes. Sustained viral response (SVR) after treatment was equal between the wildtypes and heterozygotes (54 vs. 56%). Conclusion We found a heterozygosity rate of 0.06, in line with healthy controls in other studies. Serum A1AT levels from A1AT heterozygous HCV patients are significantly lower compared with wildtype patients, although they do not discriminate on an individual level. Finally, SVR in A1AT wildtypes was not different from SVR in A1AT heterozygotes.

Clinical impact of five large-scale screening projects for chronic hepatitis B in Chinese migrants in the Netherlands.

In low‐endemic countries it is debated whether first‐generation migrants should be screened for chronic hepatitis B infection. We describe the clinical impact of five large‐scale Dutch screening projects for hepatitis B in first‐generation Chinese migrants.

T1982 Ribavirin- Rather Than PEG-Interferon-Related Factors are Predicting Non-Response to Antiviral Therapy in Naive Chronic Hepatitis C Patients

243 ENDOGENOUS ERYTHROPOIETIN RESPONSE AND PREDICTIVE FACTORS FOR ANEMIA DURING TREATMENT WITH PEG-INTERFERON ALFA-2B AND RIBAVIRIN IN CHRONIC HEPATITIS C PATIENTS L.G. van Vlerken, H. van Soest, M.P. Janssen, G.J. Boland, J.P.H. Drenth, D.M. Burger, P.D. Siersema, K.J. van Erpecum. Department of Gastroenterology and Hepatology, Julius Center for Health Sciences and Primary Care, Department of Virology, University Medical Center Utrecht, Utrecht, Department of Gastroenterology and Hepatology, Clinical Pharmacy Department, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands E-mail: g.j.boland@umcutrecht.nl

New Treatment Options for Chronic Hepatitis C

The hepatitis C virus (HCV) is an enveloped positive-stranded RNA virus that belongs to the family of flaviviridae and causes viral hepatitis type C. Since its discovery in 1989 by Houghton and colleagues, hepatitis C has been recognized as a major, public, worldwide health problem. Before 1989, the condition was known as post-transfusion hepatitis or non-A, non-B hepatitis. HCV can cause chronic hepatitis in 80% of the infected patients, demonstrated by the persistence of HCV RNA in the blood. This is a life-shortening disease associated with complex, expensive morbidity and a decrease in the quality of life.