Treatment of Chronic Hepatitis C in Older Patients

Because hepatitis C typically causes slow liver disease progression, many patients are diagnosed years after initial infection, after they have already developed advanced disease.

Two recent studies presented at the Digestive Disease Week 2007 meeting last month in Washington, DC, and one published in the March 31, 2007 advance online edition of the American Journal of Gastroenterology, looked at the relationship between older age and response to treatment for chronic hepatitis C.

The Association of German Independent Gastroenterologists, in cooperation with Roche, is conducting a nationwide observational study to determine the quality of treatment for chronic hepatitis C in routine clinical practice. Between March 2003 and May 2006, data from 11,700 patients were collected at more than 500 centers.

The researchers conducted a cross-sectional analysis of all patients older than 60 years (n = 1529; 13.1% of the entire cohort) who started a treatment with pegylated interferon plus ribavirin, assessing efficacy, tolerability, and adherence.

In the over-60 subset, 43.5% of the treated patients were male, 96.2% were Caucasian, mean age was 65.2 years, mean duration of HCV infection was 18.1 years, mean body mass index (BMI) was 26.1 kg/m², 30.9% had severe fibrosis or cirrhosis (Desmet-Scheuer stage F3/F4), 26.5% had GFR (kidney filtration rate) < 90 mL/min/1.73m², and 65.7% had concomitant diseases, the most frequent being heart disease (52.6%), diabetes (16.7%), and joint diseases (10.8%). Most (85.6%) had genotype 1, 8.9% had genotype 2, 3.1% had genotype 3, and 2.4% had genotypes 4, 5, or 6.

Results

·         As of May 2006, 82% of the treated older patients achieved early virological response (EVR) at week 12 (at least a 2-log₁₀ drop or undetectable HCV RNA).

·         About half of genotype 1 patients who completed therapy (52.3%) achieved an end-of-treatment response.

·         Among the 188 patients with adequate follow-up, 36.2% achieved sustained virological response (SVR).

·         More than one-quarter of the patients (27.8%) discontinued therapy:

o        49.1%, due to virological non-response;

o        46.2% due to poor tolerability;

o        4.7% for personal reasons;

o        2.8% lost to follow-up;

o        2.8% due to lack of adherence.

·         37% of patients -- especially those with genotype 1 -- received less than 80% of the cumulative pegylated interferon dose for 48 weeks.

·         46% received less than 80% of the cumulative ribavirin dose for 48 weeks.

Conclusion

“Comparing data of patients > 60 years with other usually studied populations reveal that due to poorer conditions at the beginning of treatment, therapy has to be discontinued very often especially for poor tolerability,” the researchers concluded.

They added that in this group of patients, careful management is necessary to prevent the escalation of adverse events leading to treatment discontinuation.

Center of Gastroenterology, Berlin; Center of Gastroenterology, Dortmund; Center for Gastroenterology and Hepatology, Duesseldorf; Center of Gastroenterology, Hannover; Center of Infectiology, Frankfurt; Center of Gastroenterology, Bad Schwalbach; Center of Gastroenterology, Krefeld; Livercenter, Berlin; Center of Gastroenterology, Goettingen; Center of Gastroenterology, Minden; Center of Gastroenterology, Schwetzingen; Center of Gastroenterology, Paderborn; Center of Gastroenterology, Herne; BU Hepatitis/HIV/Infectiology, Roche Pharma AG, Grenzach-Wyhlen, Germany.

Japanese patients with chronic hepatitis C currently being treated with interferon-based therapy are generally 10-15 years older than those in the United States. In the second study, Japanese investigators conducted a study to examine the effect of age on the efficacy and safety in patients treated with pegylated interferon plus ribavirin.

The study enrolled 158 consecutive chronic hepatitis C patients with genotype 1 and high viral load (> 100 KIU/mL). The mean age was 55 years, and about two-thirds were male. Participants were scheduled to receive 1.5 mcg/kg once-weekly pegylated interferon alpha-2b (PegIntron) plus daily weight-based ribavirin (800-1000 mg) for 48 weeks.

Patients were assessed for efficacy, safety, and tolerability every 2-4 weeks. Endpoints were SVR and dose modification or premature discontinuation of therapy due to adverse events or laboratory abnormalities.

Results

·         66 of 158 patients (42%) achieved SVR.

·         Multivariate logistic regression analysis revealed that patient age <55 years (risk ratio 5.73) and platelet count >150x10³/mcL (risk ratio 4.55) were independently associated with SVR.

·         32% of patients required dose reduction of ribavirin or pegylated interferon.

·         3% discontinued ribavirin and 19% discontinued all therapy.

·         Accordingly, just over half the patients (53%) required either dose modification or discontinuation of combination therapy due to adverse events.

·         Multivariate analysis revealed that patient age and white blood cell count were independently associated with the dose reduction or discontinuation of combination therapy.

·         Patient age (>60 years), hemoglobin level at baseline (<14 g/dL), and ribavirin apparent clearance (<10 L/hour) were significantly associated with a decrease of a hemoglobin level to below 10 g/dL.

Conclusion

“These results demonstrated that patient age was one of the important risk factors for dose modification and discontinuation of therapy that resulted in decreased efficacy,” the investigators concluded. “Aged patients may be difficult to be treated with ribavirin even in combination with peginterferon instead of standard interferon.”

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Okayama, Japan; Okayama Hepatitis C Research Group, Okayama, Okayama, Japan.

Finally, Italian researchers conducted a study to evaluate the effect of age on the treatment of chronic hepatitis C with pegylated interferon alpha plus ribavirin. They retrospectively reviewed medical records of 153 adult patients with chronic HCV infection treated with combination therapy; 30 (19.6%) were 65 years of age or older.

Results

• In multivariable analysis, all age groups above 40 years had similar odds of achieving SVR (P = 0.71).
  
  
• However, patients over 40 were significantly less likely to achieve SVR compared with younger patients:
  
  
• Age 40-49: odds ratio 0.16; P = 0.006;
• Age 50-64 years: odds ratio 0.13; P = 0.002;
• Age 64 and older: odds ratio 0.21; P = 0.037.
  
  
• The effect of age was seen in the 74 patients with genotypes 1 or 4 (P = 0.04).
  
  
• However, among the 79 patients with genotypes 2 or 3, SVR rates were relatively uniform, with no statistically significant differences.

Conclusion

In conclusion, the authors wrote, “The probability of good response to combination treatment with peginterferon alpha plus ribavirin is decreased for patients aged more than 40 years infected with genotype 1 or 4, but patients aged more than 65 had a similar rate of response to those aged 40-64 years. Combination treatment may be safely extended to elderly patients with no major contraindications.”

06/01/07

References

U Meyer, E Zehnter, S Mauss, and others. Treatment of chronic hepatitis C (CHC) with peginterferon alfa-2a (40kd) (PEG) and ribavirin (RBV) in patients older than 60 years. Digestive Disease Week 2007 (DDW 2007). Washington, DC. May 19-24, 2007. Abstract M1856.

Y Iwasaki, Y Araki, K Takaguchi, and others. Limitation of combination therapy of peginterferon and ribavirin for older patients with chronic hepatitis C. DDW 2007. Abstract M1857.

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