Research Articles 2003

HOME

JANIS AND FRIENDS HEPATITIS C WEB SITE

Research Articles 2003

	Triple therapy regimens containing amantadine offer hope for HCV nonresponders
	Extending Peginterferon Plus Ribavirin Therapy to 72 Weeks in Late Responders with Genotype 1 Chronic HCV Can Produce a Sustained Virologic Response

Triple therapy regimens containing amantadine offer hope for HCV nonresponders

2003 MAY 12 - (NewsRx.com) -- by Sonia Nichols, senior medical writer - Therapeutic

regimens that add amantadine to conventional combination interferon and ribavirin therapy may be

valuable for treating chronic hepatitis C nonresponders.

"Fifty percent of chronic hepatitis C patients are nonresponders to interferon. At present,

there are no recommended therapeutic options for nonresponders," researchers at the Second

University of Naples in Italy advised in the journal Gut.

Those researchers have completed a study of 114 chronic hepatitis C nonresponders that

suggests amantadine could broaden the outlook for those patients. In that study, L.E. Adinolfi and

colleagues randomized patients to receive two different combinations of interferon and ribavirin,

with the interferon being offered thrice weekly (group A) or daily then trice weekly (group B). A

third group received the interferon and ribavirin combination given to group B, but with additional

amantadine (group C). Patients received therapy for one year.

"The end of treatment response for groups A and B was 25% and 29%, respectively, and

for group C, (68%) (p<0.005)," reported Adinolfi and coauthors.

The sustained response rate a year after treatment ended was 6- to more than 10-fold

higher among group C patients than among those of the other two groups, weighing in at 25%. The

sustained response rates in groups A and B were only 2% and 4%, respectively (Effects of alpha

interferon induction plus ribavirin with or without amantadine in the treatment of interferon nonresponsive

chronic hepatitis C: A randomized trial. Gut, May 2003;52(5):701-705).

Triple treatment regimens that include interferon, ribavirin, and amantadine may offer

better long-term effectiveness for treating nonresponder chronic hepatitis C patients, Adinolfi's team

concluded.

The corresponding author for this study is L.E. Adinolfi, Division of Internal Medicine

and Hepatology, Faculty of Medicine, Second University of Naples, Via Cotugno 1, 80137 Napoli,

Italy.

Key points reported in this study include:

As many as half the patients who receive interferon therapy for chronic hepatitis C

will not respond to treatment

Long-term response in chronic hepatitis C patients who received a triple drug

regimen that included amantadine was significantly higher than long-term response

in patients who only received interferon and ribavirin

Triple combination regimens that include interferon, ribavirin, and amantadine

may be better for treating chronic hepatitis C nonresponders

This article was prepared by Hepatitis Weekly editors from staff and other reports.

Hepatitis C Therapy

Extending Peginterferon Plus Ribavirin Therapy to 72 Weeks in Late Responders with Genotype 1 Chronic HCV Can Produce a Sustained Virologic Response

Most HCV-infected individuals in the US have genotype 1 HCV, which is the most difficult genotype to treat successfully. In patients with HCV genotype 1, the sustained virologic response (SVR) to 48 weeks of treatment with peginterferon plus ribavirin (the current standard of care) is about 42%.

Study results suggest that one primary factor in SVR is rapid hepatitis C virus (HCV) RNA clearance, which ranges from 75% for patients who clear in 12 weeks to only 32% for those who lose HCV RNA at week 24.

Some researchers propose that extending therapy in patients who cleared HCV RNA between weeks 12 and 24 (i.e., late responders) could increase SVR.

In a Letter to the Editor of the current issue of Hepatology (May 2003), researchers at the Liver Clinic, Gastroenterology Institute, in Kaplan, Israel describe results of a small study in nine patients:

“We selected 9 patients with chronic hepatitis C who were infected with genotype 1 in treatment with pegylated interferon alfa-2b plus ribavirin who cleared HCV RNA between weeks 12 and 24 for therapy prolonged to 72 weeks. Three were men and 6 were women, with a median age of 41 ± 14.57 years. All patients had elevated alanine aminotransferase levels, positive HCV RNA, and a liver examination showing chronic hepatitis.

“Patients were treated with a mean dose of 1.0 microgram/kg of peginterferon alfa-2b once weekly (PEG-Intron) plus 800 mg/d of ribavirin (Rebetol). HCV RNA was analyzed by using a quantitative, real-time, reverse-transcriptase polymerase chain reaction technique with a lower limit of detection of 100 IU/L.

“Eight patients completed therapy and 6 months of follow-up. One patient stopped therapy at week 48 because of thyroid alterations. Table 1 shows patient characteristics and changes in HCV-RNA levels from baseline to week 12. .

Table 1. Baseline Characteristics of the 9 Patients Treated and HCV-RNA Changes in Logs From Baseline to Week 12 and HCV-RNA Decline From Baseline to Week 12
Case	Sex	Age (y)	Histology	ALT (UI/L)	HCV-RNA (UI/mL) Logs Baseline	HCV-RNA (UI/mL) Logs Week 12	HCV-RNA Decline Logs Between Baseline and Week 12
1	M	41	Moderate CAH	75	5.97	2.04	–3.93
2	M	36	Moderate CAH	186	5.40	3.00	–2.40
3	F	35	Mild CAH	95	6.23	2.68	–3.55
4	F	63	Moderate CAH	90	5.84	2.04	–3.80
5	F	61	Moderate CAH	83	6.61	3.38	–3.23
6	M	30	Moderate CAH	97	6.18	2.92	–3.31
7	F	52	Moderate CAH	104	6.23	2.81	–3.36
8	F	20	Moderate CAH	89	5.48	2.30	–3.18
9	F	52	Moderate CAH	78	5.47	2.18	–3.29
Abbreviations: ALT, alanine aminotransferase; CAH, chronic active hepatitis.

“In all patients, HCV RNA was positive at week 12 of therapy but undetectable at week 24 and throughout the 72 weeks of therapy. At week 24 of follow-up, 7 patients maintained an SVR and one relapsed (case 3).

“This study, with a small number of patients, showed that prolonged combination therapy with peginterferon and ribavirin is very useful in late virologic responders because it increases SVR. HCV-RNA determination has an important role not only in the decision to stop therapy but also in better adjusting therapy.

“Currently, nonresponders can be detected by a quantitative HCV-RNA test at week 12, showing a decline of less than 2 logs in HCV-RNA concentrations. In these patients, combination therapy should be stopped because the probabilities of a sustained response are almost nil. In patients who achieve an early virologic response, the probabilities of achieving an SVR were 80% for those who cleared HCV RNA at week 12 and sooner, and 40% for those who achieved a 2-log reduction in HCV-RNA concentrations but still remained HCV-RNA positive as a recent review of multicenter studies has shown.

“All of our patients had a 2-log decline but remained HCV-RNA positive at week 12 and, taking into account the previous results, their probabilities of achieving an SVR are lower than those patients who were HCV-RNA negative at week 12. In this subgroup of patients, with a slower decline in HCV-RNA levels, usually genotype 1 patients with high baseline viral levels, continuing therapy to 72 weeks could be the best way to ensure an SVR with acceptable tolerability and safety.

“In summary, extending therapy with peginterferon alfa plus ribavirin to 72 weeks for late virologic responders may induce a higher SVR. These results merit further prospective, randomized, controlled studies, using the optimal doses of peginterferon and ribavirin for longer duration versus the current standard 48-week therapy in this subset of patients.”

05/02/03

Reference
M Buti and others (Liver Clinic, Gastroenterology Institute, Kaplan, Israel).
Extending combination therapy with peginterferon alfa-2b plus ribavirin for genotype 1 chronic hepatitis C late responders: A report of 9 cases. Letter to the Editor. Hepatology 37 (5):1226. May 2003.

http://www.hivandhepatitis.com/hep_c/news/050203a.html

Reviewed Feb 2004