| |
How Durable is the HCV Sustained Viral Response?
|
| |
| |
by V. J. Smith, RN, BSN, MA
Article Date: 8/25/2004
10 Years of Long-Term Outcome Studies of Interferon Therapy for HCV Infection
A goal in the course of hepatitis C treatment with interferon, peginterferon and peginterferon/ribavirin combination therapy is the achievement of a Sustained Viral Response (SVR).
An SVR is defined as having undetectable levels of hepatitis C virus 6 months after the termination of a course of treatment. The percentage of patients who achieve SVR varies with patient age, genotype and viral load.
In some patients, the virus returns to detectable levels at some point after being undetectable shortly after the cessation of treatment - this is called "relapse." However, the majority of patients who achieve an SVR do not relapse.
In this article, we will review the results of several clinical studies that have examined the long-term outcomes of hepatitis C treatment; specifically, how often patients who achieve SVR subsequently experience a return of detectable levels of hepatitis C virus.
Because pegylated interferon medications were not approved for use by the FDA until 2001 (PEG-Intron) and 2002 (Pegasys), long-term outcome studies of these medications are not yet available.
1993
Researchers at the Chiba University School of Medicine in Japan examined a group of 21 patients who had been treated with alpha-interferon for 12 months.
The study found that of the 12 patients who had cleared the virus during treatment, all were virus-undetectable 3 to 5 years after the termination of treatment, and showed improved liver histology on biopsy.
1995
A study conducted by researchers at the Karolinska Institute in Stockholm, Sweden found that 14 patients who had achieved undetectable levels of virus after 6 months of interferon alfa-2b treatment remained virus-undetectable 2 years after the cessation of treatment.
These authors suggest that those patients who achieve SVR and have normalized liver enzymes are likely to have a "durable long-term response without relapse of the viremia."
1997
A somewhat larger study conducted at Hopital Beaujon in Clichy, France examined a cohort of 80 patients who had chronic hepatitis C and had a sustained virologic response to interferon-alpha therapy for up to 6 years.
The results indicated that during the entire follow-up period, 93 percent of patients had persistently normal serum ALT levels, and serum HCV RNA remained undetectable in 96 percent of patients.
Additionally, a comparison of liver biopsy samples showed a clear improvement in 94 percent of patients, and in 62 percent of patients, the last biopsy showed normal or nearly normal results.
Another study, conducted at the University of Bologna, Italy, followed 16 patients who had achieved an SVR for 36 months after the termination of treatment. All members of this cohort were found to be have normal ALT values and undetectable virus during the entire follow-up period.
1998
Researchers at the University of Toronto in Ontario, Canada followed a group of 5 patients who had achieved a sustained viral response after a course of treatment with interferon-alpha-2b for approximately 5 years.
They found that this small group remained in "serological remission" for up to 66.2 months after the completion of interferon therapy (the duration of the follow-up study).
A group of 25 patients who had responded to treatment with interferon-alpha were followed by researchers at the Ospedale San Paolo in Milan, Italy for a period of 21 to 79 months after the termination of treatment.
In this group, 22 out of 25 patients continued to test negative for both liver and serum HCV RNA, and all patients, even those who tested positively for HCV RNA, demonstrated a marked improvement in liver histology.
Researchers at the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland conducted a follow-up study of 10 patients with chronic hepatitis C who were treated with interferon-alpha-2b for 52 weeks (+/- 6 weeks).
The follow-up period ranged from 6 to 13 years, and liver biopsies were done 5 to 11 years after initiation of therapy.
Among the 5 patients who had an SVR, all remained HCV RNA negative, 4 had normal aminotransferase levels and 1had minimally elevated aminotransferase levels.
Another study, conducted at the Consiglio Nazionale delle Ricerche in Palermo, Italy, followed a group of sustained responders for up to 109 months after the completion of interferon therapy.
At the end of the follow-up period, 56 out of 62 sustained responders (90.3%) were serum HCV RNA negative.
1999
A study of 12 patients who achieved SVR after 24 weeks of interferon-alpha2b / ribavirin treatment was conducted by researchers at the Huddinge Hospital in Sweden. The study found that 11 of the 12 patients remained HCV RNA negative 2 years after the termination of treatment.
In addition, these researchers found that in 9 of the 12 patients biopsied at the 2-year follow-up, liver inflammation had disappeared completely and fibrosis had improved.
A study conducted by researchers at the Karolinska Institutet in Stockholm, Sweden examined a group of 26 patients who had achieved SVR after interferon therapy for periods ranging from 3.5 to 8.8 years.
Of the group of 26 patients, 22 patients had normal serum ALT levels, 24 patients (92 percent) were HCV RNA negative in serum, and liver biopsies performed in 23 patients 2.1 to 8.7 years after end of treatment showed no or minimal liver inflammation. Mild and probably irreversible fibrosis was seen in a few patients.
Another study, conducted at the University of Naples Federico II in Naples, Italy followed a group of 39 sustained responders for up to 73 months after interferon treatment, and found that 92 percent of the sustained responders remained HCV RNA negative throughout the study follow-up period.
An interesting study conducted at Padova University in Padova, Italy was conducted to determine if daily interferon therapy for the first 3 months of treatment was more effective than thrice-weekly interferon therapy.
Although only 9 to 12 percent of study participants achieved SVR after 6 months of interferon treatment, all of those who achieved a sustained response were found to be virus-undetectable 72 months after the conclusion of treatment.
2000
A study conducted at the Toronto Western Hospital in Toronto, Ontario, Canada examined the duration of viral response in a group of sustained responders who had been treated for 6 months with interferon-alpha for follow-up periods ranging from 6 to 92 months (average 38 months).
These researchers found that of 16 patients who were virus undetectable 6 months after the termination of treatment, 14 (88 percent) remained undetectable at final follow-up.
2002
Researchers at Aker University Hospital in Oslo, Norway conducted 5-year follow-up study of 27 IV drug users who had demonstrated a sustained response to interferon treatment for HCV infection.
The follow-up period ranged from 13 to 82 months (median 64). At the end of follow-up, only one member of the group had detectable virus, and this individual had continued to inject drugs and reported frequent needle sharing.
2003
A study by a group of researchers at the Karol Marcinkowski University of Medical Sciences in Poznan, Poland investigated outcomes in a group of children treated with interferon for hepatitis C infection.
In the group of 4 children who demonstrated a sustained response 6 months after the completion of treatment, all remained virus undetectable throughout the 2-year follow-up period.
Another interesting study was conducted by researchers at the Hotel-Dieu, Hepatology Unit in Lyon, France. This study was conducted to determine the long-term effect of interferon / ribavirin combination on HCV-infected liver transplant recipients.
Fourteen transplant recipients with chronic hepatitis after liver transplant were treated with interferon / ribavirin combination therapy, and demonstrated a sustained viral response.
At the end of a 3-year follow up period, 13 of the 14 patients (93 percent) were found to be HCV RNA negative, and 12 of the 14 patient showed a clear improvement in liver histology.
2004
Researchers at the Hannover Medical School in Hannover, Germany followed a group of 31 sustained responders who had been treated for HCV infection for 52 to 224 weeks (median 135 weeks).
At the end of the study period, all patients remained virus-undetectable, and all but one had normalized liver enzymes.
Note from Jules Levin: 4-year follow-up of a large number of patients treated with Pegasys+ribavirin (Copegus) found 98% of patients who achieved an SVR and maintained undetectable virus load for 6 months additional remained without detectable virus for the 4 years of followup. Experts in the field call these patients "cured" or their HCV has been apparently eradicated.
Conclusions
a.. Patients who demonstrate non-detectable levels of hepatitis C virus in serum 6 months after the completion of interferon-based treatment will remain "clear" in roughly 90 to 100% of cases.
b.. Long-term eradication of the virus results in significant improvements in liver enzyme levels.
c.. Long-term suppression or eradication of virus in serum results in significant improvements in inflammation, and in many cases, a reduction or elimination of liver fibrosis.
d.. Although not specifically discussed in this article, the studies reviewed also indicated that significant improvement in liver histology and normalization of aminotransferases can occur during the course of treatment even if the patient relapses after the termination of treatment.
Source
Hosoda K, et al. Long-term effects of alpha-interferon for treatment of chronic hepatitis C in terms of histological changes with aminotransferase normalization and hepatitis C virus RNA seroconversion. Gastroenterol Jpn. 1993 May;28 Suppl 5:115-7.
Reichard O, et al. Two-year biochemical, virological, and histological follow-up in patients with chronic hepatitis C responding in a sustained fashion to interferon alfa-2b treatment. Hepatology. 1995 Apr;21(4):918-22.
Marcellin P, et al. Long-term histologic improvement and loss of detectable intrahepatic HCV RNA in patients with chronic hepatitis C and sustained response to interferon-alpha therapy. Ann Intern Med 1997 Nov 15:127(10):875-81.
De Mitri MS, et al. Complete eradication of hepatitis C virus after interferon treatment for chronic hepatitis C. Ital J Gastroenterol Hepatol. 1997 Jun;29(3):255-61.
Sim H, et al. Durability of serological remission in chronic hepatitis C treated with interferon-alpha-2b. Am J Gastroenterol. 1998 Jan;93(1):39-43.
Larghi A, et al. Clinical significance of hepatic HCV RNA in patients with chronic hepatitis C demonstrating long-term sustained response to interferon-alpha therapy. J Med Virol. 1998 May;55(1):7-11.
Lau DT, et al. 10-year follow-up after interferon-alpha therapy for chronic hepatitis C. Hepatology 1998 Oct;28(4):1121-7
Camma C, et al. Long-term course of interferon-treated chronic hepatitis C. J Hepatol. 1998 Apr;28(4):531-7.
Schvarcz R, et al. Histological and virological long-term outcome in patients treated with interferon-alpha-2b and ribavirin for chronic hepatitis C. J Viral Hepat. 1999 May;6(3):237-42.
Reichard O, et al. Long-term follow-up of chronic hepatitis C patients with sustained virological response to alpha-interferon. J Hepatol. 1999 May;30(5):783-7.
Morisco F, et al. Clinical outcome of chronic hepatitis C in patients treated with interferon: comparison between responders and non-responders. Ital J Gastroenterol Hepatol. 1999 Aug-Sep;31(6):454-8.
Chemello L et al. Comparison of thrice weekly vs. daily human leucocyte interferon-alpha therapy for chronic hepatitis C. TVVH Study Group. J Viral Hepat 1999 Jul;6(4):321-7.
Collier JD, et al. Long term follow-up of patients with chronic hepatitis C treated with interferon alpha. Can J Gastroenterol. 2000 Jul-Aug;14 Suppl B:77B-80B.
Dalgard O, et al. Treatment of chronic hepatitis C in injecting drug users: 5 years' follow-up. Eur Addict Res. 2002 Jan;8(1):45-9.
Mozer-Lisewska I, et al. Virus genotype 1b and long-term response to interferon alpha monotherapy in children with chronic hepatitis C. Eur J Pediatr. 2003 Nov;162(11):755-9. Epub 2003 Aug 22.
Bizollon T, et al. Long term histological improvement and clearance of intrahepatic hepatitis C virus RNA following sustained response to interferon-ribavirin combination therapy in liver transplanted patients with hepatitis C virus recurrence. Gut. 2003 Feb;52(2):283-7.
Wiegand J, et al. Long-term follow-up after successful interferon therapy of acute hepatitis C. Hepatology. 2004 Jul;40(1):98-107.
V.J. Smith is a Registered Nurse with a Bachelor's degree in Nursing and a Master's degree in Clinical Psychology, and has experience in oncology, critical care and hospice, nursing management, counseling and clinical administration.
http://www.hepatitisneighborhood.com/content/understanding_hepatitis/treating_hepatitisc_2034.aspx
|
|
| |
| |
|
|
|
